Organometallic complex catalyst

ABSTRACT

An organometallic complex catalyst that makes it possible to obtain a higher yield of a desired product than conventional catalysts in a cross-coupling reaction. The organometallic complex catalyst has a structure represented by formula (1) and is for use in a cross-coupling reaction. In formula (1), M is the coordination center and represents a metal atom such as Pd or an ion thereof. R1, R2, and R3 may be the same or different and are a substituent such as a hydrogen atom. R4, R5, R6, and R7 may be the same or different and are a substituent such as a hydrogen atom. X represents a halogen atom. R8 represents a substituent that has a π bond and 3-20 carbon atoms. With regard to the electron-donating properties of R1-R7 with respect to the coordination center M of the ligand containing R1-R7 that is indicated in formula (2), R1-R7 are arranged in combination such that the TEP value obtained from infrared spectroscopy shifts toward the low frequency side compared to the TEP value of the ligand of formula (2-1).

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No.16/466,413, filed on Jun. 4, 2019, which is a 371 of InternationalApplication No. PCT/JP2017/043890, filed on Dec. 6, 2017, which is basedupon and claims the benefit of priority from the prior Japanese PatentApplication No. 2016-237942, filed on Dec. 7, 2016 and Japanese PatentApplication No. 2016-237941, filed on Dec. 7, 2016, the entire contentsof which are incorporated herein by reference.

TECHNICAL FIELD

The present invention relates to an organometallic complex catalyst foruse in a cross-coupling reaction. More specifically, the presentinvention relates to an organometallic complex catalyst for use in across-coupling reaction which has a ligand having a nitrogen-containingheterocyclic carbene structure.

BACKGROUND ART

Aromatic amines are widely used in medicines, pesticides and electronicmaterials.

As methods for synthesizing the aromatic amines, a method forsynthesizing through a C—N coupling reaction by using a palladiumcomplex catalyst has been reported (for example, Non-Patent Documents 1to 3).

Furthermore, in order to proceed the C—N coupling reaction moreefficiently, there has been proposed a Pd complex catalyst having aligand which contains a structure of nitrogen-containing heterocycliccarbene (N-Heterocyclic Carbene, hereinafter referred to as “NHC”, asoccasion demand).

The ligand containing the structure of the NHC was firstly isolated ascrystalline NHC by Arduengo et al. in 1991, and its structure wasconfirmed by X-ray crystal structure analysis (see, for example,Non-Patent Document 4, and the following chemical formula (P1)).

[In the (P1), the cat. represents a predetermined catalyst, THFrepresents tetrahydrofuran, DMSO represents dimethyl sulfoxide.]

It has been known that the Pd complex catalyst having the ligandcontaining the structure of the NHC (hereinafter referred to as “NHC—Pdcomplex catalyst”, as occasion demand) has a high capability ofcoordinating to palladium because the NHC has a strong a donor propertyand a weak r acceptor property, and is stable to air and water in thecomplex state. In addition, many examples which were used as catalystsfor various cross-coupling reactions and showed very high performance inthe activity have been reported.

As the NHC—Pd complex catalyst, for example, an NHC—Pd complex catalystnamed “PEPPSI” by Organ et al. in 2005 has been proposed (for example,Non-Patent Document 5). This PEPPSI is useful as a coupling reactioncatalyst, and is used in many reactions including the Suzuki couplingreaction (see, for example, Non-Patent Documents 6 to 8 and thefollowing chemical formula (P2)).

[In the (P2), R represents a hydrocarbon group (including a hydrocarbongroup consisting of carbon and hydrogen, a hydrocarbon group containingan —NH₂ group, an —SH group, and an —OH group), an —NH₂ group, an —SHgroup and an —OH group, the “PEPPSI” is an abbreviation of PyridineEnhanced Precatalyst Preparation Stabilization Initiation, and has achemical structure represented by the following formula (P3).]

Here, in the present description, the “Pr” represents an isopropylgroup.

Furthermore, various NHC—Pd complex catalysts have been proposed byNolan et al. in 2006. For example, it has been reported that, when anNHC—Pd complex catalyst (“IPrPd (allyl)”) represented by the followingformula (P4) was used, for example, as a catalyst for C—N couplingreaction represented by the following formula (P6), even at roomtemperature, the reaction proceeds well (see, for example, Non-Patentdocuments 9 to 10).

Here, in the present description, the “IPr” represents a ligand(1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) having an NHCstructure represented by the following formula (P5).

[In the (P6), R, R′ and R″ may be the same as or different from eachother, and a hydrocarbon group (including a hydrocarbon group consistingof carbon and hydrogen, a hydrocarbon group containing an —NH₂ group, an—SH group and an OH group), an —NH₂ group, an —SH group and an —OHgroup, the “^(t)Bu” represents tert-butyl group (tertiary butyl group)].

Incidentally, the present applicant submits, as publications where theabove-mentioned publicly-known inventions are described, the followingpublications:

PRIOR ART DOCUMENT Non-Patent Document

-   Non-Patent Document 1: Kosugi, M., Kameyama, M., Migita. T. Chem.    Lett. 1983, 927-   Non-Patent Document 2: Guram, A. S., Rennels, R. A., Buchwald, S. L.    Angew. Chem., Int. Ed. Engl. 1995, 34, 1348-   Non-Patent Document 3: Louie, J., Hartwig, J. F. Tetrahedron Lett.    1995, 36(21), 3609-   Non-Patent Document 4: Louie, J., Arduengo, A. J. Am. Chem. Soc.    1991, 113, 361-   Non-Patent Document 5: Organ, M. G. Rational catalyst design and its    application in sp³-sp³ couplings. Presented at the 230th National    Meeting of the American Chemical Society, Washington, D C, 2005;    Abstract 308.-   Non-Patent Document 6: Organ, M. G., Avola, S., Dubovyk, L., Hadei,    N., Kantchev, E. A. B., OBrien, C., Valente, C. Chem. Eur. J. 2006,    12, 4749-   Non-Patent Document 7: Ray, L., Shaikh, M. M., Ghosh, P. Dalton    trans. 2007, 4546-   Non-Patent Document 8: Obrien, C. J., Kantchev, E. A. B., Valente,    C., Hadei, N., Chass, G. A., Lough, A., Hopkinson, A. C.,    Organ, M. G. Chem. Eur. J. 2006, 12, 4743-   Non-Patent Document 9: Marion, M., Navarro, O., Stevens, J. M, E.,    Scott, N. M., Nolan, S. P. J. Am. Chem. Soc. 2006, 128, 4101-   Non-Patent Document 10: Navarro, O., Marion, N., Mei, J.,    Nolan, S. P. Chem. Eur. J. 2006, 12, 5142

SUMMARY OF THE INVENTION Problem to be Solved by the Invention

However, from the viewpoint of obtaining a higher yield of a desiredproduct in the cross-coupling reaction, the present inventors have foundthat there is still room for improvement, even with the aforementionedcatalysts of the prior arts.

The present invention has been made in view of such technicalcircumstances, and an object of the present invention is to provide anorganometallic complex catalyst capable of obtaining a higher yield of adesired object than conventional catalysts in a cross-coupling reaction.

Another object of the present invention is to provide a ligand having anitrogen-containing heterocyclic carbene structure which is a structuralmaterial of the organometallic complex catalyst of the presentinvention.

Furthermore, an object of the present invention is to provide a methodfor preparing an organometallic complex catalyst for cross-couplingreaction by using the ligand of the present invention.

Means to Solve the Problems

As a result of intensive studies to solve the aforementioned problems,the present inventors have found that it is effective that theorganometallic complex catalyst has a structure represented by thefollowing formula (1) where a substituent “—SiR¹R²R³” containing asilicon atom (hereinafter referred to as “silyl group” as occasiondemand) is bonded to the carbon atom at the 4- or 5-position in the NHCstructure of the imidazole ring (hereinafter referred to as “backbonecarbon” as occasion demand).

Furthermore, with respect to the ligands where the silyl group is bondedto the backbone carbon at the 4- or 5-position in the NHC structure ofthe imidazole ring, when comparing the electron-donating property to thecentral metal by measuring TEP values (Tolman electronic parameter)[cm⁻¹] obtained by an infrared spectroscopy, the present inventors havefound that the organometallic complex catalyst containing the ligandwhich has a higher electron-donating property to the central metal thanthe IPr ligand (formula (P5)) is effective, and then the presentinvention has been completed.

More specifically, the present invention includes the followingtechnical elements.

Namely, according to the present invention, it is possible to provide anorganometallic complex catalyst for use in a cross-coupling reaction,which has a structure represented by the following formula (1).

Here, in the formula (1), M is a coordination center and represents anyone of metal atoms selected from the group consisting of Pd, Pt, Rh, Ruand Cu, or an ion thereof.

Further, R¹, R² and R³ may be the same or different, and each representsat least one substituent selected from the group consisting of ahydrogen atom, an alkyl group, an alkoxy group, alkenyl group, analkynyl group and an aryl group.

Furthermore, R⁴, R⁵, R⁶ and R⁷ may be the same or different, and eachrepresents at least one substituent selected from a hydrogen atom, ahalogen atom, an alkyl group, an alkoxy group, an alkenyl group, analkynyl group, an aryl group, a hydroxy group, hydroxylate group, athiocarboxyl group, a dithiocarboxyl group, a sulfo group, a sulfinogroup, an oxycarbonyl group, a carbamoyl group, a hydrazinocarbonylgroup, an amidino group, a cyano group, an isocyano group, a cyanatogroup, an isocyanato group, a thiocyanato group, an isothiocyanatogroup, a formyl group, an oxo group, a thioformyl group, a thioxo group,a mercapto group, an amino group, an imino group, a hydrazino group, anaryloxy group, a sulfide group, a nitro group and a silyl group.

Further, in the formula (1), X represents a halogen atom which iscapable of coordinating to the coordination center M.

Furthermore, R⁸ represents a substituent having a π bond and 3 to 20carbon atoms which is capable of coordinating to the coordination centerM.

Provided that, with regard to electron-donating property with respect tothe coordination center M, R¹, R², R³, R⁴, R⁵, R⁶ and R⁷ are so combinedand arranged that a TEP value (Tolman electronic parameter) [cm⁻¹]obtained by an infrared spectroscopy of a ligand having anitrogen-containing heterocyclic carbene structure represented by thefollowing formula (2) which contains R¹ to R⁷, sifts toward a lowfrequency side compared to the TEP value [cm⁻¹] of a ligand representedby the formula (2-1).

Here, in the formula (2), R¹, R², R³, R⁴, R⁵, R⁶ and R⁷ represent thesame substituents as R¹, R², R³, R⁴, R⁵, R⁶ and R⁷ in the formula (1).

Further, in the formula (2-1), R⁴, R⁵, R⁶ and R⁷ represent the samesubstituents as R⁴, R⁵, R⁶ and R⁷ in the formula (1).

The organometallic complex catalyst of the present invention having theaforementioned constitution can give a higher yield of the desiredproduct than the conventional catalysts such as the NHC—Pd complexcatalyst exemplified in Non-Patent Documents 1 to 10 mentioned above inthe cross-coupling reaction.

Though the detailed mechanism by which the organometallic complexcatalyst of the present invention can obtain a high yield of the desiredproduct has not been found, the present inventors speculate as follows.

Namely, the present inventors speculate that, though the conventionalcatalysts have the structure where a hydrogen atom is bonded to thebackbone carbon at the 4- or 5-position in the structure of NHC of theimidazole ring (structure of IPr ligand (formula (P5)), theorganometallic complex catalyst of the present invention has thestructure where the aforementioned silyl group (—SiR¹R²R³) is bonded tothe backbone carbon at the 4- or 5-position in the structure of NHC, andthe difference may contribute to the improvement of the yield of thedesired product.

In addition, as described later, the present inventors measured the TEPvalue obtained by an infrared absorption spectrum with respect to a Rhcarbonyl complex where the portion of the -MR⁸X of the organometalliccomplex of the present invention is substituted by —Rh(CO)₂Cl.

As a result, the present inventors have found that among the ligandsrepresented by the formula (2), the organometallic complex catalysthaving the ligand which has the TEP value shifted to a lower wave numberside than the IPr ligand (formula (P5)), i.e., the ligand having ahigher electron donating property than the IPr ligand (formula (P5)) cangive a higher yield of the desired product than the conventionalcatalysts such as the NHC—Pd complex catalyst (IPrPd (allyl))represented by the formula (P4).

Then, based on these results, the present inventors believe that, whenhaving the structure where the silyl group (—SiR¹R²R³) is bonded to thebackbone carbon at the 4- or 5-position in the NHC structure of theimidazole ring, and the structure where the TEP value satisfies theconditions described above, the catalytically active species M⁰ (zerovalence) in the catalytic reaction is stabilized, and thus, the desiredproduct can be obtained in high yield (see, for example, Example 1 andExample 2 described later).

In the organometallic complex of the present invention, it is preferablethat the TEP value [cm⁻¹] of the ligand having the nitrogen-containingheterocyclic carbene structure represented by the following formula (2)is a value calculated from a stretching frequency [cm⁻¹] of a carbonylgroup obtained from an infrared absorption spectrum measured on an Rhcarbonyl complex represented by the following formula (1-1), which is acomplex where, in the formula (1), the portion of the -MR⁸X issubstituted by —Rh(CO)₂Cl.

In this case, the TEP value can be obtained according to the followingequation (E1).

[Equ. 1]

TEP[cm⁻¹]=ν_(CO) ^(av/Ni) [cm⁻¹]=0.8001ν_(CO) ^(av/Rh) [cm⁻¹]+420.0[cm⁻¹]  (E1)

Here, in the equation (E1), the v_(CO) ^(av/Rh) represents an arithmeticmean value calculated from a stretching frequency [cm⁻¹] of the carbonylgroup obtained from the infrared absorption spectrum measured on the Rhcarbonyl complex, and the v_(CO) ^(av/Ni) represents an arithmetic meanvalue [cm⁻¹] (=TEP value [cm⁻¹]) calculated from a stretching frequencyof the carbonyl group obtained from the infrared absorption spectrummeasured on the Ni carbonyl complex.

In the present invention, as a method of evaluating the electrondonating property to the central metal of the ligand which contains theNHC structure of the organometallic complex catalyst by employing theTEP value calculated according to the above equation (E1), the methoddescribed in the Non-Patent document “T. Droge and F. Glorius, Angew.Chem. Int. Ed., 2010, 49, 6940” is employed.

The TEP value (Tolman electronic parameter) is originally the stretchingfrequency of the carbonyl group obtained from the infrared absorptionspectrum of a Ni carbonyl complex where the coordination center is Ni.However, the Ni carbonyl complex is so toxic that it is difficult for ameasuring person to carry out the measuring procedures of the infraredabsorption spectrum. Thus, by using the stretching frequency of thecarbonyl group obtained from the infrared absorption spectrum of the Rhcarbonyl complex and the equation (E1) in this way, it is possible forthe measuring person to carry out the measuring procedures of theinfrared absorption spectrum in the environment where the safety isimproved.

Further, from the viewpoint of obtaining the effects of the presentinvention more reliably, the organometallic complex catalyst of thepresent invention is preferably used in a C—N cross-coupling reaction.

Furthermore, from the viewpoint of obtaining the effect of the presentinvention more reliably, it is preferable that the organometalliccomplex catalyst of the present invention has a structure represented bythe following formula (3), the formula (4) or the formula (5).

Here, in the formulae (3) to (5), Pr represents an isopropyl group, Merepresents methyl group.

Further, the present invention provides a ligand which has anitrogen-containing heterocyclic carbene structure represented by thefollowing formula (2) and is a structural material of an organometalliccomplex catalyst for use in a cross-coupling reaction having a structurerepresented by the following formula (1).

Here, in the formula (1) and the formula (2), M is a coordination centerand represents any one of metal atoms selected from the group consistingof Pd, Pt, Rh, Ru and Cu, or an ion thereof.

R¹, R² and R³ may be the same or different, and each represents at leastone substituent selected from the group consisting of a hydrogen atom,an alkyl group, an alkoxy group, alkenyl group, an alkynyl group and anaryl group.

R⁴, R⁵, R⁶ and R⁷ may be the same or different, and each represents atleast one substituent selected from a hydrogen atom, a halogen atom, analkyl group, an alkoxy group, an alkenyl group, an alkynyl group, anaryl group, a hydroxy group, hydroxylate group, a thiocarboxyl group, adithiocarboxyl group, a sulfo group, a sulfino group, an oxycarbonylgroup, a carbamoyl group, a hydrazinocarbonyl group, an amidino group, acyano group, an isocyano group, a cyanato group, an isocyanato group, athiocyanato group, an isothiocyanato group, a formyl group, an oxogroup, a thioformyl group, a thioxo group, a mercapto group, an aminogroup, an imino group, a hydrazino group, an aryloxy group, a sulfidegroup, a nitro group and a silyl group.

X represents a halogen atom which is capable of coordinating to thecoordination center M.

R⁸ represents a substituent having a π bond and 3 to 20 carbon atomswhich is capable of coordinating to the coordination center M.

Provided that, with regard to electron-donating property with respect tothe coordination center M, R¹, R², R³, R⁴, R⁵, R⁶ and R⁷ are so combinedand arranged that a TEP value (Tolman electronic parameter) [cm⁻¹]obtained by an infrared spectroscopy of a ligand having anitrogen-containing heterocyclic carbene structure represented by thefollowing formula (2) which contains R¹ to R⁷, sifts toward a lowfrequency side compared to the TEP value [cm⁻¹] of a ligand representedby the formula (2-1).

Here, in the formula (2-1), R⁴, R⁵, R⁶ and R⁷ represent the samesubstituents as R⁴, R⁵, R⁶ and R⁷ in the formula (1).

The ligand of the present invention is suitable to the constitutionalmaterial of the aforementioned organometallic complex catalyst of thepresent invention.

Since the ligand of the present invention has the structure where thesilyl group (—SiR¹R²R³) is substituted by the hydrogen atom bonded tothe backbone carbon at the 4- or 5-position in the 5-membered ring ofthe ligand having the NHC structure such as the IPr, and the structurewhere the TEP value satisfies the conditions described above, theelectron donating property to the metal at the coordination center canbe enhanced. Thus, the present inventors speculate that the oxidativeaddition reaction in the coupling reaction (preferably C—N couplingreaction) can be promoted.

Further, in the organometallic complex of the present invention, it ispreferable that the TEP value of the ligand having thenitrogen-containing heterocyclic carbene structure represented by thefollowing formula (2) is a value calculated from a stretching frequencyof a carbonyl group obtained from an infrared absorption spectrummeasured on an Rh carbonyl complex represented by the following formula(1-1), which is a complex where, in the formula (1), the portion of the-MR⁸X is substituted by —Rh(CO)₂Cl.

In this case, the TEP value can be obtained according to theaforementioned equation (E1).

Furthermore, the present invention can provide a method for preparing anorganometallic complex catalyst for use in a cross-coupling reactionhaving a structure represented by the following formula (1), whichincludes:

a first step for synthesizing a ligand which has a nitrogen-containingheterocyclic carbene structure represented by the following formula (2),

a second step for synthesizing a complex comprising the coordinationcenter M in the formula (1) and a halogen X and a substituent R⁸, and

a third step for reacting the ligand having the NHC structure obtainedby the first step and the complex obtained by the second step.

Here, in the formulae (1) and (2), M is a coordination center andrepresents any one of metal atoms selected from the group consisting ofPd, Pt, Rh, Ru and Cu, or an ion thereof.

R¹, R² and R³ may be the same or different, and each represents at leastone substituent selected from the group consisting of a hydrogen atom,an alkyl group, an alkoxy group, alkenyl group, an alkynyl group and anaryl group.

R⁴, R⁵, R⁶ and R⁷ may be the same or different, and each represents atleast one substituent selected from a hydrogen atom, a halogen atom, analkyl group, an alkoxy group, an alkenyl group, an alkynyl group, anaryl group, a hydroxy group, hydroxylate group, a thiocarboxyl group, adithiocarboxyl group, a sulfo group, a sulfino group, an oxycarbonylgroup, a carbamoyl group, a hydrazinocarbonyl group, an amidino group, acyano group, an isocyano group, a cyanato group, an isocyanato group, athiocyanato group, an isothiocyanato group, a formyl group, an oxogroup, a thioformyl group, a thioxo group, a mercapto group, an aminogroup, an imino group, a hydrazino group, an aryloxy group, a sulfidegroup, a nitro group and a silyl group.

X represents a halogen atom which is capable of coordinating to thecoordination center M.

R⁸ represents a substituent having a π bond and 3 to 20 carbon atomswhich is capable of coordinating to the coordination center M;

Provided that, with regard to electron-donating property with respect tothe coordination center M, R¹, R², R³, R⁴, R⁵, R⁶ and R⁷ are so combinedand arranged that a TEP value (Tolman electronic parameter) [cm⁻¹]obtained by an infrared spectroscopy of a ligand having anitrogen-containing heterocyclic carbene structure represented by thefollowing formula (2) which contains R¹ to R⁷, sifts toward a lowfrequency side compared to the TEP value [cm⁻¹] of a ligand representedby the formula (2-1).

Here, in the formula (2-1), R⁴, R⁵, R⁶ and R⁷ represent the samesubstituents as R⁴, R⁵, R⁶ and R⁷ in the formula (1).

The present inventors have found that, in the process of preparing anorganometallic complex catalyst, it is effective to solve theaforementioned problem by using the ligand having the structure of theNHC represented by formula (2), more specifically, the ligand (ligand ofthe present invention) having the structure where the silyl group(—SiR¹R²R³) is bonded to the backbone carbon at the 4- or 5-position inthe NHC structure of the imidazole ring, and the structure where the TEPvalue satisfies the conditions described above in the first step.

According to the present invention, it is possible to provide a methodfor reliably preparing the organometallic complex catalyst for thecross-coupling reaction where the ligand is used, that is, theorganometallic complex catalyst which can give the desired product in ahigher yield than the conventional catalysts in the cross-couplingreaction.

Further, according to the method for preparation of the presentinvention, it is possible to prepare more easily and more reliably theorganometallic complex catalyst for the cross-coupling reaction wherethe ligand of the present invention is used, that is, the organometalliccomplex catalyst of the present invention which can give the desiredproduct in a higher yield than the conventional catalysts in thecross-coupling reaction.

According to the method for preparation of the present invention, it ispossible to prepare the ligand of the present invention which has thestructure where the silyl group is substituted by the hydrogen atombonded to the backbone carbon at the 4- or 5-position in the 5-memberedring of the ligand having the NHC structure such as the IPr, and thestructure where the TEP value satisfies the conditions described above.

Conventionally, though the synthesis of the ligand having the NHCstructure where a hydrogen atom of the backbone carbon is substituted byanother substituent requires a multistep synthesis step, in the methodfor preparation of the present invention, it is possible to synthesize,in relatively few synthesis steps and under relatively mild conditions,the ligand where the silyl group is bonded to the backbone carbon at the4- or 5-position in high yield, on the basis of the ligand such as IPretc. where a hydrogen atom is bonded to the backbone carbon at the 4- or5-position. Moreover, in the method for preparation of the presentinvention, various types of silyl groups can be introduced into thehydrogen moiety which is bonded to the backbone carbon at the 4- or5-position by changing the silicon reagent of the raw material.

For example, according to the method for preparation of the presentinvention, as shown in the following formula (C1), the synthesis stepsrequired to prepare the final product (the NHC—Pd complex or the NHC—Rhcomplex having the ligand where a hydrogen on the backbone carbon of theligand having the NHC structure is substituted by the silyl group) fromIPr can be reduced to relatively few steps, i.e. three.

Effects of the Invention

According to the present invention, an organometallic complex catalystcapable of obtaining a higher yield of a desired object thanconventional catalysts in a cross-coupling reaction can be provided.

Further, according to the present invention, a ligand having anitrogen-containing heterocyclic carbene structure which is a structuralmaterial of the organometallic complex catalyst of the present inventionwhich can obtain a higher yield of a desired object than conventionalcatalysts in a cross-coupling reaction can be provided.

Furthermore, according to the present invention, a method for morereliably preparing the organometallic complex catalyst for thecross-coupling reaction where the ligand of the present invention isused, that is, the organometallic complex catalyst which can give thedesired product in a higher yield than the conventional catalysts in thecross-coupling reaction can be provided.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph which shows the ¹H NMR spectrums obtained with respectto the ligands having the NHC structure represented in the reactionformulae (R1) to (R3).

FIG. 2 is a graph which shows the ¹H NMR spectrums obtained with respectto the ligands of “IPr” and “^(TMS)IPr” having the NHC structure.

FIG. 3 is a graph which shows the ¹H NMR spectrum obtained with respectto the organometallic complex catalyst {^(TMS)IPrPd(allyl)} of Example1.

FIG. 4 is a graph which shows the MALDI-TOF-MS spectrum obtained withrespect to the organometallic complex catalyst {^(TMS)IPrPd(allyl)} ofExample 1.

FIG. 5 is a graph which shows the ¹H NMR spectrums obtained with respectto the ligands of “IPr” and “^(TEOS)IPr” having the NHC structure.

FIG. 6 is a graph which shows the ¹H NMR spectrum obtained with respectto the organometallic complex catalyst {^(TEOS)PrPd(allyl)} ofComparative Example 1.

FIG. 7 is a graph which shows the MALDI-TOF-MS spectrum obtained withrespect to the organometallic complex catalyst {^(TEOS)IPrPd(allyl)} ofComparative Example 1.

FIG. 8 is a graph which shows the ¹H NMR spectrum obtained with respectto the ligand having the NHC structure of the organometallic complexcatalyst of Example 2.

FIG. 9 is a graph which shows the ¹H NMR spectrum obtained with respectto the organometallic complex catalyst of Example 2.

FIG. 10 is an ORTEP drawing obtained with respect to the organometalliccomplex catalyst {^(TMS)IPrPd(allyl)} of Example 1.

FIG. 11 is an ORTEP drawing obtained with respect to the organometalliccomplex catalyst {^(TEOS)IPrPd(allyl)} of Comparative Example 1.

FIG. 12 is ORTEP drawings obtained with respect to the organometalliccomplex catalyst {^(TMS)IPrPd(allyl)} of Example 1 and theorganometallic complex catalyst {^(TEOS)IPrPd(allyl)} of ComparativeExample 1.

FIG. 13 is a graph which shows the ¹H NMR spectrums obtained withrespect to IPr, ^(TMS)IPr, ^(TEOS)IPr.

FIG. 14 is a conceptual diagram which shows the reaction mechanismclarified in the C—N coupling reaction where an organic Pd complexcatalyst is used.

MODE FOR CARRYING OUT THE INVENTION

Preferable embodiments of the present invention are described in detailhereunder.

<Configuration of Organometallic Complex Catalyst>

The organometallic complex catalyst of the present embodiment is anorganometallic complex catalyst for use in a cross-coupling reaction,preferably a C—N cross-coupling reaction which has a structurerepresented by the following formula (1).

Further, the ligand of the present invention is a ligand which is astructural material of an organometallic complex catalyst of the presentembodiment and has a nitrogen-containing heterocyclic carbene structurerepresented by the following formula (2).

Here, in the formula (1), M is a coordination center and represents anyone of metal atoms selected from the group consisting of Pd, Pt, Rh, Ruand Cu, or an ion thereof.

Further, R¹, R² and R³ may be the same or different, and each representsat least one substituent selected from the group consisting of ahydrogen atom, an alkyl group, an alkoxy group, alkenyl group, analkynyl group and an aryl group.

Furthermore, R⁴, R⁵, R⁶ and R⁷ may be the same or different, and eachrepresents at least one substituent selected from a hydrogen atom, ahalogen atom, an alkyl group, an alkoxy group, an alkenyl group, analkynyl group, an aryl group, a hydroxy group, hydroxylate group, athiocarboxyl group, a dithiocarboxyl group, a sulfo group, a sulfinogroup, an oxycarbonyl group, a carbamoyl group, a hydrazinocarbonylgroup, an amidino group, a cyano group, an isocyano group, a cyanatogroup, an isocyanato group, a thiocyanato group, an isothiocyanatogroup, a formyl group, an oxo group, a thioformyl group, a thioxo group,a mercapto group, an amino group, an imino group, a hydrazino group, anaryloxy group, a sulfide group, a nitro group and a silyl group.

Further, in the formula (1), X represents a halogen atom which iscapable of coordinating to the coordination center M.

Furthermore, R⁸ represents a substituent having a π bond and 3 to 20carbon atoms which is capable of coordinating to the coordination centerM.

Provided that, with regard to electron-donating property with respect tothe coordination center M, R¹, R², R³, R⁴, R⁵, R⁶ and R⁷ are so combinedand arranged that a TEP value (Tolman electronic parameter) [cm⁻¹]obtained by an infrared spectroscopy of a ligand having anitrogen-containing heterocyclic carbene structure represented by thefollowing formula (2) which contains R¹ to R⁷, sifts toward a lowfrequency side compared to the TEP value [cm⁻¹] of a ligand representedby the formula (2-1).

Here, in the formula (2), R¹, R², R³, R⁴, R⁵, R⁶ and R⁷ represent thesame substituents as R¹, R², R³, R⁴, R⁵, R⁶ and R⁷ in the formula (1).

Further, in the formula (2-1), R⁴, R⁵, R⁶ and R⁷ represent the samesubstituents as R⁴, R⁵, R⁶ and R⁷ in the formula (1).

The organometallic complex catalyst of the present embodiment which hasthe ligand of the present embodiment having the aforementionedconstitution can give a higher yield of the desired product than theconventional catalysts such as the NHC—Pd complex catalyst exemplifiedin Non-Patent Documents 1 to 10 mentioned above in the cross-couplingreaction.

Though the detailed mechanism by which the organometallic complexcatalyst of the present embodiment can obtain a high yield of thedesired product has not been found, the present inventors speculate asfollows.

Namely, the present inventors speculate that, though the conventionalcatalysts have the structure where a hydrogen atom is bonded to thebackbone carbon at the 4- or 5-position in the structure of NHC of theimidazole ring (structure of IPr ligand (formula (P5)), theorganometallic complex catalyst of the present invention has thestructure where the aforementioned silyl group (—SiR¹R²R³) is bonded tothe backbone carbon at the 4- or 5-position in the structure of NHC, andthe difference may contribute to the improvement of the yield of thedesired product.

In addition, as described later, the present inventors measured the TEPvalue obtained by an infrared absorption spectrum with respect to a Rhcarbonyl complex where the portion of the -MR⁸X of the organometalliccomplex of the present embodiment is substituted by —Rh(CO)₂Cl.

As a result, the present inventors have found that among the ligandsrepresented by the formula (2), the organometallic complex catalysthaving the ligand which has the TEP value shifted to a lower wave numberside than the IPr ligand (formula (P5)), i.e., the ligand having the NHCstructure and a higher electron donating property than the IPr ligand(formula (P5)) can give a higher yield of the desired product than theconventional catalysts such as the NHC—Pd complex catalyst (IPrPd(allyl)) represented by the formula (P4).

Then, based on these results, the present inventors believe that, whenhaving the structure where the silyl group (—SiR¹R²R³) is bonded to thebackbone carbon at the 4- or 5-position in the NHC structure of theimidazole ring, and the structure where the TEP value satisfies theconditions described above, the catalytically active species M⁰ (zerovalence) in the catalytic reaction is stabilized, and thus, the desiredproduct can be obtained in high yield (see, for example, Example 1 andExample 2 described later).

In the organometallic complex of the present embodiment, it ispreferable that the TEP value [cm⁻¹] of the ligand having thenitrogen-containing heterocyclic carbene structure represented by thefollowing formula (2) is a value calculated from a stretching frequency[cm⁻¹] of a carbonyl group obtained from an infrared absorption spectrummeasured on an Rh carbonyl complex represented by the following formula(1-1), which is a complex where, in the formula (1), the portion of the-MR⁸X is substituted by —Rh(CO)₂Cl.

In this case, the TEP value can be obtained according to the followingequation (E1).

[Equ. 2]

TEP[cm⁻¹]=ν_(CO) ^(av/Ni) [cm⁻¹]=0.8001ν_(CO) ^(av/Rh) [cm⁻¹]+420.0[cm⁻¹]  (E1)

Here, in the equation (E1), the v_(CO) ^(av/Rh) represents an arithmeticmean value calculated from a stretching frequency [cm⁻¹] of the carbonylgroup obtained from the infrared absorption spectrum measured on the Rhcarbonyl complex, and the v_(CO) ^(av/Ni) represents an arithmetic meanvalue [cm⁻¹] (=TEP value [cm⁻¹]) calculated from a stretching frequencyof the carbonyl group obtained from the infrared absorption spectrummeasured on the Ni carbonyl complex.

In the present invention, as a method of evaluating the electrondonating property to the central metal of the ligand which contains theNHC structure of the organometallic complex catalyst by employing theTEP value calculated according to the above equation (E1), the methoddescribed in the Non-Patent document “T. Dr&ouml; ge and F. Glorius,Angew. Chem. Int. Ed., 2010, 49, 6940” is employed.

The TEP value (Tolman electronic parameter) is originally the stretchingfrequency of the carbonyl group obtained from the infrared absorptionspectrum of a Ni carbonyl complex where the coordination center is Ni.However, the Ni carbonyl complex is so toxic that it is difficult for ameasuring person to carry out the measuring procedures of the infraredabsorption spectrum. Thus, by using the stretching frequency of thecarbonyl group obtained from the infrared absorption spectrum of the Rhcarbonyl complex and the equation (E1) in this way, it is possible forthe measuring person to carry out the measuring procedures of theinfrared absorption spectrum in the environment where the safety isimproved.

Here, from the viewpoint of obtaining the effects of the presentinvention more reliably, the coordination center M is preferably Pd.

From the viewpoint of obtaining the effects of the present inventionmore reliably, at least one of R¹, R² and R³ is preferably an alkylgroup or an alkoxyl group. More preferable is an alkyl group or alkoxylgroup having 1 to 3 carbon atoms.

From the viewpoint of obtaining the effects of the present inventionmore reliably, at least one of R⁴, R⁵, R⁶ and R⁷ is preferably an alkylgroup having 1 to 3 carbon atoms.

From the viewpoints of obtaining the effects of the present inventionmore reliably and of availability of the raw material, X is preferablyCl among the halogen atoms.

From the viewpoint of obtaining the effects of the present inventionmore reliably, R⁸ is preferably a substituent having 3 to 10 carbonatoms which has a π bond capable of coordinating to the coordinationcenter M, more preferably a substituent having 3 to 9 carbon atoms whichhas a π bond capable of coordinating to the preferred coordinationcenter Pd.

Further, from the viewpoint of obtaining the effects of the presentinvention more reliably, the organometallic complex catalyst of thepresent invention which has the ligand of the present invention as aconfiguration material is preferably used for the C—N cross-couplingreaction.

Furthermore, from the viewpoint of obtaining the effects of the presentinvention more reliably, the organometallic complex catalyst of thepresent invention preferably has the structure represented by thefollowing formula (3), formula (4) or formula (5).

Here, in the formulae (3) to (5), ^(i)Pr represents an isopropyl group,Me represents methyl group.

The present embodiment can provide the organometallic complex catalystcapable of obtaining a higher yield of a desired object thanconventional catalysts in a cross-coupling reaction, and the ligandwhich is the structural material of the organometallic complex catalys.

<Preferred Embodiment of Method for Preparing Organometallic ComplexCatalyst>

The organometallic complex catalyst according to the present embodimentcan be prepared, without any particular limitation, by combining andoptimizing the known methods for synthesizing ligands and methods forsynthesizing complex catalysts.

The method for preparing the organometallic complex catalyst of thepresent embodiment includes:

a first step for synthesizing a ligand which has the NHC structurerepresented by the following formula (2),

a second step for synthesizing a complex comprising the coordinationcenter M in the formula (1) and a halogen X and a substituent R⁸, and

a third step for reacting the ligand having the NHC structure obtainedby the first step and the complex obtained by the second step.

Furthermore, the method for preparing the organometallic complexcatalyst of the present embodiment may further include a fourth step forpurifying the organometallic complex catalyst of the present embodimentobtained after the third step. As the purification procedure of thefourth step, there can be employed a known purification technique. Forexample, a recrystallization method by using a predetermined solvent maybe employed.

According to the method for preparing the organometallic complexcatalyst of the present embodiment of the present embodiment, it ispossible to provide a method for reliably preparing the organometalliccomplex catalyst for the cross-coupling reaction where the ligand isused, that is, the organometallic complex catalyst which can give thedesired product in a higher yield than the conventional catalysts in thecross-coupling reaction.

Further, according to the method for preparation of the presentembodiment, it is possible to prepare more easily and more reliably theorganometallic complex catalyst for the cross-coupling reaction wherethe ligand of the present embodiment is used, that is, theorganometallic complex catalyst of the present embodiment which can givethe desired product in a higher yield than the conventional catalysts inthe cross-coupling reaction.

According to the method for preparation of the present embodiment, it ispossible to prepare the ligand of the present invention which has thestructure where the silyl group is substituted by the hydrogen atombonded to the backbone carbon at the 4- or 5-position in the 5-memberedring of the ligand having the NHC structure such as the IPr, and thestructure where the TEP value satisfies the conditions described above.

Conventionally, though the synthesis of the ligand having the NHCstructure where a hydrogen atom of the backbone carbon is substituted byanother substituent requires a multistep synthesis step, in the methodfor preparation of the present invention, it is possible to synthesize,in relatively few synthesis steps and under relatively mild conditions,the ligand where the silyl group is bonded to the backbone carbon at the4- or 5-position in high yield, on the basis of the ligand such as IPretc. where a hydrogen atom is bonded to the backbone carbon at the 4- or5-position. Moreover, in the method for preparation of the presentinvention, various types of silyl groups can be introduced into thehydrogen moiety which is bonded to the backbone carbon at the 4- or5-position by changing the silicon reagent of the raw material.

For example, according to the method for preparation of the presentembodiment, as shown in the following formula (C1), the synthesis stepsrequired to prepare the final product (the organic Pd complex catalystor the organic Rh complex catalyst having the ligand where a hydrogen onthe backbone carbon of the ligand having the NHC structure issubstituted by the silyl group) from IPr can be reduced to relativelyfew steps, i.e. three.

Here, in the formula (CO), R¹, R² and R³ are the same as R¹, R² and R³in the aforementioned formula (1).

EXAMPLE

In the following, the present invention is more specifically explainedby referring working examples, but the present invention is not limitedto the following working examples.

(Explanation of Analyzers)

When synthesizing the organometallic complex catalysts of Examples 1 to3 and Comparative Examples 2 and 2 described below, the followinganalyzers were used for the analysis.

[NMR Spectrum]

For the ¹H NMR, ¹³C{¹H} NMR, ²⁹Si{¹H} NMR spectrum measurement, BrukerBiospin Avance 400 (400 MHz) available from Bruker Co. Ltd. was used. Inall of the measurements of the ligands, a dehydrated heavy solvent wasused. This is to prevent the decomposition of the ligand.

For the ¹³C{¹H} CPMAS, ²⁹Si{¹H} CPMAS spectrum measurement, BrukerBiospin Avance 400WB (400 MHz) available from Bruker Co. Ltd. wasused.[Mass Spectrometry]

For the MALDI-TOF-MS spectrum measurement, Bruker AUTOFLEX™ TOF/TOF wasused.

[Elementary Analysis]

For the elementary analysis, CE Instruments EÅ1110 elemental analyzeravailable from CE Instruments Co., Ltd. was used.

[Single-Crystal X-Ray Crystal Structure Analysis]

For the single-crystal X-ray crystal structure analysis, Bruker SMARTAPEX CCD available from Bruker Co., Ltd. was used. Analysis calculationwas performed by using Crystal Structure available from RIGAKU Co., Ltd.

[GC Measurement]

For the gas chromatography (GC) measurement, GC-2014 available fromShimadzu Corporation was used. As the capillary column, TC-1 (60 m) wasused.

[Nitrogen Adsorption Measurement]

For the nitrogen adsorption measurement, a high-accuracy specificsurface area/pore distribution measuring apparatus (Bel sorp mini)available from Bell Japan Co., Ltd. was used.

[EDX Measurement]

For the EDX measurement, a fluorescent X-ray analyzer (EDX-800HS)available from Shimadzu Corporation was used.

[IR Measurement]

For the IR measurement, NICOLET 6700 Diamond ATR (smart orbit) availablefrom Thermo Scientific Co., Ltd. was used.

[Column Device]

A medium pressure preparative solution chromatograph YFLC-Al-580available from Yamazen Co., Ltd. was used, and a Hi-Flash Column Silicagel available from Yamazen Co., Ltd. was used as a silica column.

(Explanation of Commercially Available Reagents)

The following commercially available reagents were used in the synthesisand analysis of the organometallic complex catalysts of Examples 1 to 3and Comparative Examples 2 to 2 described below.

Reagents available from Kanto Chemical Co., Ltd.: acetic acid, potassiumtert-butoxide, n-butyllithium, chlorobenzene, 1,2-dimethoxyethane

Reagents available from Sigma-Aldrich Japan reagent:chlorotriethoxysilane, mesitylene, heavy chloroform, MCM-41

Reagents available from Tokyo Chemical Industrry Co., Ltd.:2,6-diisopropylaniline, chlorotrimethylsilane, 2,4,6-trimethylaniline,1,3-di-tert-butylimidazol-2-ylidene, cinnamyl chloride

Reagents available from Wako Pure Chemical Corporation: methanol, ethylacetate, tetrahydrofuran, hexane, toluene, dodecane, dibutyl aniline,allyl chloride, 40% glyoxal solution, paraformaldehyde

Reagent available from N.E. CHEMCAT CORPORATION: Palladium chloride

Reagent available from Fuji Silyl Co., Ltd.: Q-6

Reagents available from ISOTEC Co., Ltd.: heavy benzene, heavy THF

Example 1

An organometallic complex catalyst {trade name “NTMS-PDA”, availablefrom N.E. CHEMCAT CORPORATION (hereinafter referred to as“^(TMS)IPrPd(allyl)” as occasion demand)} was prepared. This^(TMS)IPrPd(allyl) is an organometallic complex catalyst shown in theformula (3).

The organometallic complex catalyst {^(TMS)IPrPd(allyl)} of Example 1was synthesized by the following procedures.

[Example 1 First Step-1] Synthesis of Ligand “IPr” Having the NHCStructure

Starting from 2,6-diisopropylaniline as a starting material, a ligand“IPr” having the NHC structure represented by the formula (P5) describedabove, i.e. {1,3-bis (2,6-diisopropylphenyl) imidazol-2-ylidene} wassynthesized.

Specifically, referring to the procedures described in the academicarticles (Tang, P., Wang, W., Ritter, T. J. Am. Chem. Soc. 2011, 133,11482, and Pompeo, M., Froese, R. D. J., Hadei, N., Organ, M. G. Angew.Chem. Int. Ed. 2012, 51, 11354), synthesis was carried out through thethree steps shown in the following reaction schemes (R1) to (R3).Identification was carried out by using ¹H NMR to confirm that IPr andan intermediate product were synthesized.

In the reaction scheme (R1), MeOH represents methanol, and HOAcrepresents acetic acid.

The synthesis procedure of the intermediate product 1 in the reactionscheme (R1) is explained.

In a 50 mL eggplant flask, 6.00 g (33.8 mmol) of 2,6-diisopropylaniline,30 mL of methanol and 0.31 mL (3.5 mol %) of acetic acid were added andheated to 50° C. Next, a mixed solution of 2.40 g (0.5 eq.) of glyoxal40% aq. and 10 mL of methanol were added dropwise. The mixture turnedfrom a clear colorless solution to a clear yellow solution as the mixedsolution was dropped. After stirring at 50° C. for 15 minutes, thetemperature was returned to room temperature and stirring was furthercarried out for 11 hours. When cooling to room temperature, a yellowsolid was precipitated. After the completion of the reaction, filtrationwas carried out by using a membrane filter, and the solid was washedwith methanol. Since a small amount of the desired intermediate product1 was dissolved in methanol when washed, the filtrate was recovered andthe solvent was removed, and the obtained solid was washed again with asmall amount of methanol and filtered. The yellow solids obtained in thefirst time and the second time were combined and dried.

The yielded amount of the intermediate product 1 (yellow powdery solid)in the formula (R1) was 5.49 g, and the yield was 86.0%.

In the reaction scheme (R2), TMSCl represents chlorotrimethylsilane, andEtOAc represents ethyl acetate.

The synthesis procedure of the intermediate product 2 in the reactionscheme (R2) is explained.

In a 500 mL eggplant flask, 3.80 g (10.08 mmol) of (1E, 2E)-1,2-bis(2,6-diisopropylphenylimino)ethane, 0.32 g (10.66 mmol) ofparaformaldehyde, 83 mL of ethyl acetate were added and heated to 70° C.The mixture was in the form of a yellow slurry-like solution. Next, amixed solution of 0.34 mL (10.66 mmol) of chlorotrimethylsilane and 8 mLof ethyl acetate was added dropwise over 20 minutes. Thereafter,stirring was continued at 70° C. for 2 hours. The color of the solventturned from yellow to orange. After the completion of the reaction, thereaction product was dipped in an ice water to be cooled to 0° C. Aftercooling, filtration was carried out by using a membrane filter, and thesolid was washed with ethyl acetate. Thereafter, a vacuum drying wascarried out to obtain a pale pink powdery solid.

The yielded amount of the intermediate product 2 (white powdery solid)in the formula (R2) was 3.96 g, and the yield was 92.5%.

In the reaction scheme (R3), ^(t)BuOK represents (CH₃)₃COK, and THFrepresents tetrahydrofuran.

The synthesis procedure of the product 3 “IPr” in the reaction scheme(R3) is explained.

Under an inert gas atmosphere, 0.43 g (1.01 mmol) of 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride, 0.14 g (1.21 mmol) oftBuOK, 5 mL of dehydrated THF were added in a 25 mL Schlenk, and stirredat room temperature for 3.5 hours. The color of the solution was changedfrom white to brown. After the completion of the reaction, the solventwas removed, and then the solid was dissolved by adding 5 mL ofdehydrated toluene and heating and stirring at 50° C. Thereafter, 5 mLof dehydrated hexane was added. In order to remove the salt (KCl) in thesolution, Celite filtration was carried out in a glove box. A brownclear solution was obtained. A brown powdery solid was obtained byremoving the solvent and carrying out the vacuum drying.

The yielded amount of the product 3 “IPr” in the reaction scheme (R3)(brown powdery solid) was 0.30 g, and the yield was 78.0%.

Identification was carried out by using ¹H NMR, and it was confirmedthat IPr and the intermediate product (intermediate product 1 in theformula (R1), intermediate product 2 in the formula (R2)) weresynthesized.

The ¹H NMR spectra obtained for each of the ligands having the NHCstructure shown in the reaction schemes (R1) to (R3) are shown inFIG. 1. FIG. 1(A) shows the ¹H NMR spectrum of the intermediate product1 in the reaction scheme (R1). CDCl₃ was used as a deuterated solvent(deuterated solvent). FIG. 1(B) shows the ¹H NMR spectrum of theintermediate product 2 in the reaction scheme (R2). CD₃CN was used as adeuterated solvent. FIG. 1(C) shows the ¹H NMR spectrum of IPr shown bythe product 3 in the reaction scheme (R3). C₆D₆ was used as a deuteratedsolvent.

The measurement results of the intermediate product 1 are shown below.

¹H NMR (CDCl₃, 400 MHz): δ8.10 (s, 2H), 7.20-7.13 (m, 6H), 2.94 (m, 4H),1.21 (d, 24H, J=6.8 Hz)

The measurement results of the intermediate product 2 are shown below.

¹H NMR (CD₃CN, 400 MHz): δ9.35 (s, 1H), 7.87 (s, 2H), 7.65 (t, 2H, J=7.5Hz), 7.47 (d, 4H, J=7.7 Hz), 2.41 (m, 4H), 1.26 (d, 12H, J=6.8 Hz), 1.20(d, 12H, J=6.8 Hz)

The measurement results of the product 3 “IPr” are shown below.

¹H NMR (C₆D₆, 400 MHz): δ7.31-7.27 (m, 2H), 7.19-7.17 (m, 4H), 6.61 (s,2H), 2.96 (m, 4H), 1.29 (d, 12H, J=6.8 Hz), 1.18 (d, 12H, J=7.0 Hz)

[Example 1 First Step-2] Synthesis of a Ligand where TrimethylsilylGroup is Bonded to the Carbon at 4-Position in the NHC Structure of IPr

A ligand {ligand represented by the following formula (7)} having theNHC structure used for the organometallic complex catalyst representedby the formula (3) of Example 1 was synthesized by using the ligand IProbtained in the aforementioned [First step-1].

Specifically, modifying the procedure described in the academic article(Wang, Y., Xie, Yaming., Abraham, M. Y., Wei, P., Schaeferlll, H. F.,Schleyer, P. R., Robinson, G. H. J. Am. Chem. Soc. 2010, 132, 14370),through the two steps represented by the following reaction scheme (R4),synthesis of the ligand 5 represented by the formula (7) (hereinafterreferred to as “^(TMS)IPr” 5 as occasion demand) where trimethylsilylgroup (—SiMe₃, hereinafter referred to as “TMS group” as occasiondemand) is bonded to the carbon at 4-position in the NHC structure ofIPr (reactant 3).

In the reaction scheme (R4), ^(n)BuLi represents CH₃CH₂CH₂CH₂Li, and THFrepresents tetrahydrofuran.

The synthesis procedure of the intermediate product 4 (Li—IPr) in thereaction scheme (R4) is explained.

Firstly, 10.79 g (27.62 mmol) of IPr (reactant 3) and 100 mL ofdehydrated hexane were added to a 300 mL eggplant-shaped flask in aglove box, and the obtained solution was stirred at room temperature for30 minutes. Next, ^(n)BuLi was slowly added dropwise to the obtainedsuspension, and reaction was continued with stirring overnight to reactat room temperature. The light brown slurry-like solution was changed toa yellow slurry-like solution. After the completion of the reaction, thereaction solution was filtered by a membrane filter and washed withdehydrated hexane. The resulting yellow powder solid {intermediateproduct 4 (Lithiodide: Li—IPr) in the reaction scheme (R4)} was dried.

The yielded amount of the intermediate product 4 (yellow powder solid)in the reaction scheme (R4) was 10.0 g, and the yield was 92.0%.

Next, the synthesis procedure of the product 5 (^(TMS)IPr) in thereaction scheme (R4) is explained.

Firstly, 0.78 g (1.98 mmol) of the intermediate product 4 (Li—IPr) and25 mL of dehydrated THF were added and dissolved in a 50 mL Schlenk in aglove box. Next, 0.26 mL (2.04 mmol) of chlorotrimethylsilane (ClSiMe₃,hereinafter referred to as “ClTMS” as occasion demand) was slowly addeddropwise, allowed to react for 25 minutes, and after the completion ofthe reaction, the solvent was removed.

In a glove box, 10 mL of dehydrated toluene was added to the solidproduct and dissolved, and the obtained solution was transferred to acentrifuge tube. The solution in the centrifuge tube was centrifuged at4000 rpm for 6 minutes at room temperature to separate the salt (LiCl).Next, the obtained filtrate was passed through a filter (available fromadvantec Co., Ltd., 0.2 μm) and separated into a 50 mL Schlenk. Next,the solvent was removed to obtain a yellow powder solid (^(TMS)IPr, thatis, the desired ligand 5).

The yielded amount of the product 5 “^(TMS)IPr” (yellow powder solid) inthe reaction scheme (R4) was 0.901 g, and the yield was 98.9%.

Identification was carried out by using ¹H NMR, and it was confirmedthat the lithiation of the hydrogen atom bonded to the carbon at the4-position in the NHC structure of IPr (reactant 3) proceeds, and^(TMS)IPr (desired ligand 5) was synthesized.

The ¹H NMR spectra obtained for each of the ligands of IPr (reactant 3)and ^(TMS)IPr (desired ligand 5) having the NHC structure are shown inFIG. 2. FIG. 2(A) shows the ¹H NMR spectrum of IPr (reactant 3). C₆D₆was used as a deuterated solvent (deuterated solvent). FIG. 2(B) showsthe ¹H NMR spectrum of ^(TMS)IPr (desired ligand 5). C₆D₆ was used as adeuterated solvent.

The measurement results of the reaction product 5 ^(TMS)IPr (desiredligand 5) are shown below.

¹H NMR (C₆D₆, 400 MHz): δ=7.33-7.27 (m, 2H), 7.21-7.17 (m, 4H), 6.89 (s,2H), 3.04 (m, 2H), 2.84 (m, 2H), 1.40 (d, 6H, J=6.8 Hz), 1.28 (d, 12H,J=6.8 Hz, 6.9 Hz), 1.18 (d, 6H, J=6.9 Hz), 0.05 ppm (s, 9H)

From the results of ¹H NMR shown in FIG. 2(A) and FIG. 2(B), it wasconfirmed that, since the TMS group was bonded to the carbon at the4-position in the NHC structure of IPr (reactant 3), the proton peakderived from —CH of the ^(i)Pr group became left-right asymmetric andsplit into two.

Further, consumption of the raw material was confirmed, and the peakderived from the methyl group of TMS group was observed in the vicinityof 0 ppm. It was confirmed that ^(TMS)IPr (desired ligand 5) wassynthesized because the chemical shift and the integral value were inagreement with the literatures. In addition, it was confirmed that thelithiation of IPr (reactant 3) by ^(n)BuLi was sufficiently advanced.

[Example 1 Second Step] Synthesis of Complex Containing CoordinationCenter M, Halogen X, and Substituent R⁸

Referring to Non-Patent Document 9, according to the reactionrepresented by the following reaction scheme (R5), π-allylPd complex 13{(allyl)palladium(II) chloride, hereinafter referred to as“[(allyl)PdCl₂]₂” as occasion demand} of a Pd source was synthesized.

The synthesis procedure of the π-allylPd complex 13 “[(allyl)PdCl₂]₂” inthe reaction scheme (R5) is explained.

Distilled water (260 mL) was added to a 500 mL Schlenk, and Ar wasbubbled for 30 minutes.

Next, PdCl₂ (2.14 g, 12.0 mmol) and KCl (1.89 g, 24.0 mmol) were addedand stirred for 1 hour at room temperature. Before and after thestirring, the solution changed from a slurry-like solution to a clearbrown solution. Allyl chloride (2.96 mL, 36.0 mmol) was added dropwiseto this solution, and the mixture was further stirred overnight at roomtemperature to allow the reaction of the reaction scheme (R5) toproceed. After the completion of the reaction, extraction was carriedout 5 times with chloroform (30 mL), and the removed chloroform wasdried over MgSO₄. Next, the obtained solution was filtered and thesolvent was removed to obtain a yellow solid {π-allylPd complex 13}.

The yielded amount of the π-allylPd complex 13 (yellow powder solid) was2.09 g, and the yield was 94.9%.

Identification was carried out by using ¹H NMR, and it was decided thatthe desired product i.e. the π-allylPd complex 13 {[(allyl)PdCl₂]₂} wassynthesized because the chemical shift and the integral value were inagreement with the Non-Patent Document 9.

The measurement results of the π-allylPd complex 13 {[(allyl)PdCl₂]₂}are shown below.

¹H NMR (CDCl₃, 400 MHz): δ=5.45 (m, 2H), 4.10 (d, 4H, J=6.7 Hz), 3.03(d, 4H, J=12.1 Hz)

[Example 1 Third Step] Reaction of Ligand Having the NHC StructureObtained in the First Step with the Complex Obtained in the Second Step>

The organometallic complex catalyst “^(TMS)IPrPd(allyl)15” of Example 1was synthesized, according to the following reaction scheme (R6), byreacting the ligand (^(TMS)IPr) having the NHC structure obtained in thefirst step with the π-allylPd complex 13 {[(allyl)PdCl₂]₂} obtained inthe second step.

In the third step, the reaction conditions are independently examined bythe present inventors.

In a glove box, 0.90 g (1.95 mmol) of the ligand (^(TMS)IPr) having theNHC structure obtained in the first step and 15 mL of dehydrated THFwere added to a 50 mL Schlenk. Next, 0.36 g (0.98 mmol) of the π-allylPdcomplex {[(allyl)PdCl₂]₂} obtained in the second step and 10 mL ofdehydrated THF were added to a 20 mL vial. The solution of the π-allylPdcomplex 13 was added dropwise to the solution of ^(TMS)IPr 5. Theresulting solution was stirred at room temperature for 1 hour. Beforeand after the stirring, the color of the solution was changed fromorange to brown. Next, the solution was passed through a powder ofactivated carbon to remove the Pd black produced by the reaction. Atthis time, the color of the solution was changed to yellow after passingthrough the activated carbon. Next, THF was completely removed from theresulting solution. Next, a small amount of dehydrated hexane was addedand powdered. The resulting solid was washed with hexane to give ayellow solid {reaction product 15 in the reaction scheme (R6), i.e.,^(TMS)IPrPd(allyl)}.

[Example 1 Fourth Step] Purification of Organometallic Complex CatalystObtained after Third Step

After the third step, with respect to the yellow solid{^(TMS)IPrPd(allyl) 15}, the purification was performed by subjecting torecrystallization treatment by using hexane etc.

Incidentally, this ^(TMS)IPrPd(allyl) 15 was synthesized for the firsttime by the present inventors as the organometallic complex catalystused for the cross-coupling reaction.

The yielded amount of ^(TMS)IPrPd(allyl) 15 (yellow powder solid) was0.84 g, and the yield was 66.8%.

Example 1 Identification

The ^(TMS)IPrPd(allyl) 15 was identified by ¹H NMR, ¹³C{¹H} NMR,²⁹Si{¹H} NMR, MALDI-TOF-MS and elemental analysis.

The measurement results of the ^(TMS)IPrPd(allyl) 15 are shown below.

FIG. 3 shows the spectrum of ¹H NMR obtained for the organometalliccomplex catalyst {^(TMS)IPrPd(allyl) 15} of Example 1. FIG. 4 shows thespectrum of MALDI-TOF-MS obtained for the organometallic complexcatalyst {^(TMS)IPrPd(allyl) 15} of Example 1. Table 1 shows the resultsof the elemental analysis.

¹H NMR (CDCl₃, 400 MHz): δ 7.37-7.44 (m, 2H), 7.23-7.28 (m, 4H), 7.18(s, 1H), 4.80 (m, 1H), 3.93 (d, 1H, J=7.2 Hz), 3.12 (m, 2H), 2.97 (m,2H), 2.82 (d, 1H, J=13.5 Hz), 2.75 (m, 1H), 1.59 (d, 1H, J=11.8 Hz),1.36 (m, 12H), 1.19 (m, 12H), 0.09 (s, 9H)

¹³C{¹H} NMR (CDCl₃, 100 MHz): δ 188.2, 146.5, 146.2, 145.9, 145.6,137.6, 136.1, 135.8, 133.4, 130.0, 129.8, 129.7, 124.2, 124.1, 123.7,114.2, 73.2, 50.0, 28.8, 28.4, 28.2, 26.5, 25.7, 25.6, 25.3, 24.7, 26.1,23.3, 0.1

²⁹Si{¹H} NMR (CDCl₃, 80 MHz): δ −8.12

TABLE 1 C₃₃H₄₉ClN₂PdSi C [%] H [%] N [%] Calculated value 61.57 7.674.35 Measured value 61.56 7.64 4.14

From the results of ¹H NMR, with respect to ^(TMS)IPrPd(allyl) 15, apeak derived from the allyl group was observed, and the integrated valuewas consistent with the desired structure. In addition, one clean signalwas observed from the ²⁹Si{¹H} NMR. The detailed assignment of ¹H NMRand ¹³C {¹H} NMR are determined by ¹H-¹H correlation, ¹H-¹³Ccorrelation, ¹³C DEPT spectrum.

As shown in Table 1, it is determined that the desired compound^(TMS)IPrPd(allyl) 15 was synthesized, because the calculated value andthe measured value according to the elementary analysis are almostidentical (difference within 0.3%).

Further, from the results of MALDI-TOF-MS shown in FIG. 4, it wasobserved that Cl was removed from Pd by a laser. The result ofMALDI-TOF-MS suggests that the ligand having the NHC structure is boundto Pd, and from this viewpoint as well, it was judged that the desired^(TMS)IPrPd(allyl) 15 could be synthesized.

Comparative Example 1

The organometallic complex catalyst represented by the formula (4){trade name “NTEOS-PDA”, available from N.E. CHEMCAT CORPORATION(hereinafter referred to as “^(TEOS)IPrPd(allyl)” as occasion demand)was prepared.

The organometallic complex catalyst {^(TEOS)IPrPd(allyl)} of ComparativeExample 1 was synthesized according to the following procedure.

[Comparative Example 1 First Step-1] Synthesis of Ligand “IPr” Havingthe NHC Structure

The IPr was synthesized according to the same procedures andidentification methods as in the procedures and identification methodsdescribed in [Example 1 First Step-1] of Example 1.

[Comparative Example 1 First Step-2] Synthesis of Ligand HavingTriethoxysilyl Group Bonded to Carbon at 4-Position in NHC Structure ofIPr

A ligand {ligand represented by the following formula (8)} having theNHC structure which was used in Comparative Example 1 represented by theformula (4) was synthesized by using the ligand IPr obtained in theaforementioned [First Step-1].

Specifically, through the two steps represented by the followingreaction scheme (R7), synthesis of the ligand 6 represented by theformula (8) (ligand having the NHC structure which constitutes theorganometallic complex catalyst represented by the formula (4) and theformula (6), hereinafter referred to as “^(TEOS)IPr” as occasion demand)where triethoxylsilyl group (—Si(OEt)₃, hereinafter referred to as “TEOSgroup” as occasion demand) is bonded to the carbon at 4-position in theNHC structure of IPr (reactant 3).

In the reaction scheme (R7), ^(n)BuLi represents CH₃CH₂CH₂CH₂Li, and THFrepresents tetrahydrofuran.

The synthesis procedure of the intermediate product 4 (Li—IPr) in thereaction scheme (R7) is explained. The intermediate product 4 (Li—IPr)in the reaction scheme (R7) was synthesized according to the samesynthesis procedures as the synthesis procedures of the intermediateproduct 4 (Li—IPr) in the reaction scheme (R4) described in [Example 1First Step-2] of Example 1.

Next, the synthesis procedure of the reaction product 6 (^(TEOS)IPr) inthe reaction scheme (R7) is explained.

Firstly, 3.28 g (8.32 mmol) of the intermediate product 4 (Li—IPr) and65 mL of dehydrated THF were added and dissolved in a 100 mL eggplantflask in a glove box. Next, 1.68 mL (8.57 mmol) of chlorotriethoxysilane(ClSi(OEt)₃, hereinafter referred to as “ClTEOS” as occasion demand) wasslowly added dropwise, allowed to react for 20 minutes. During thereaction, the yellow solution was changed to the brown solution. Afterthe completion of the reaction, the solvent was removed.

In a glove box, 20 mL of dehydrated hexane was added to the obtainedviscous product and transferred to a centrifuge tube. The centrifugingwas carried out at 4000 rpm for 6 minutes at room temperature toseparate the salt (LiCl). Next, the obtained filtrate was passed througha filter (available from advantec Co., Ltd., 0.2 μm) and separated intoa 50 mL Schlenk. Next, the solvent was removed to obtain a brownoil-like solution (^(TEOS)IPr, that is, the desired ligand 6).

The yielded amount of the product 5 “^(TEOS)IPr” (brown oil-likesolution) in the reaction scheme (R7) was 4.44 g, and the yield was96.9%.

Identification was carried out by using ¹H NMR, ¹³C{¹H} NMR,²⁹Si{¹H}NMR, and it was confirmed that the lithiation of the hydrogenatom bonded to the carbon at the 4-position in the NHC structure of IPr(reactant 3) proceeds, and ^(TEOS)IPr (desired ligand 6) wassynthesized.

The ¹H NMR spectra obtained for each of the ligands of IPr (reactant 3)and ^(TEOS)IPr (desired ligand 6) having the NHC structure are shown inFIG. 5. FIG. 5(A) shows the ¹H NMR spectrum of IPr (reactant 3). C₆D₆was used as a deuterated solvent (deuterated solvent). FIG. 5(B) showsthe ¹H NMR spectrum of ^(TEOS)IPr (desired ligand 6). C₆D₆ was used as adeuterated solvent.

The measurement results of ^(TEOS)IPr are shown below.

¹H NMR (C₆D₆, 400 MHz): δ7.32-7.28 (m, 2H), 7.26 (s, 1H), 7.23-7.18 (m,4H), 3.57 (q, 4H), 3.03 (m, 2H), 2.95 (m, 2H), 1.38 (t, 12H), 1.29 (d,6H), 1.18 (d, 6H), 1.03 (t, 9H, J=7.0 Hz)

¹³C{¹H} NMR (C₆D₆, 100 MHz): δ164.9, 146.3, 140.1, 139.1, 138.8, 134.4,133.0, 129.0, 128.6, 126.0, 124.3, 123.8, 123.3, 58.8, 29.1, 28.8, 25.7,24.5, 23.9, 22.7, 18.1

²⁹Si{¹H} NMR (C₆D₆, 80 MHz): δ −65.4

From the results of ¹H NMR shown in FIG. 5(A) and FIG. 5(B), it wasconfirmed that, as similar to the case that the TMS group was bonded tothe carbon at the 4-position in the NHC structure of IPr (reactant 3),since the TEOS group was bonded to the carbon at the 4-position in theNHC structure of IPr (reactant 3), the proton peak derived from —CH ofthe ^(i)Pr group became left-right asymmetric and split into two.

Further, consumption of the raw material was confirmed, and the peaksderived from the ethoxy group (—OEt group) of TEOS group were observedin the vicinity of 1.1 ppm and 3.6 ppm. From this, it was confirmed that^(TEOS)IPr (desired ligand 6) was synthesized. Furthermore, it wasconfirmed that the proton of the 5-position carbon is sifted in thedownfield by introducing a silyl group to the carbon at the 4-positionin the NHC structure of IPr (reactant 3).

In addition, the yields of IPr (reactant 3), the intermediate product 4where the hydrogen atom bonded to the carbon at the 4-position in theNHC structure of IPr (reactant 3) is substituted by Li, and ^(TEOS)IPr(desired ligand 6) are shown in the reaction scheme (R7).

[Comparative Example 1 Second Step] Synthesis of Complex ContainingCoordination Center M, Halogen X, and Substituent R⁸

Referring to Non-Patent Document 9, according to the reactionrepresented by the following reaction scheme (R5), The π-allylPd complex13 {[(allyl)PdCl₂]₂} was synthesized according to the same proceduresand identification methods as in the procedures and identificationmethods described in [Example 1 Second Step] of Example 1.

[Comparative Example 1 Third Step] Reaction of Ligand Having the NHCStructure Obtained in the First Step with the Complex Obtained in theSecond Step>

The organometallic complex catalyst “^(TEOS)IPrPd(allyl)16” ofComparative Example 1 was synthesized, according to the followingreaction scheme (R6), by reacting the ligand (^(TEOS)IPr) having the NHCstructure obtained in the first step with the π-allylPd complex{[(allyl)PdCl₂]₂} obtained in the second step.

In the third step, the reaction conditions are independently examined bythe present inventors.

In a glove box, 4.44 g (8.06 mmol) of the ligand (^(TEOS)IPr) having theNHC structure obtained in the first step and 15 mL of dehydrated THFwere added to a 50 mL Schlenk. Next, 1.47 g (4.02 mmol) of the π-allylPdcomplex 13 {[(allyl)PdCl₂]₂} obtained in the second step and 20 mL ofdehydrated THF were added to a 50 mL vial. The solution of the π-allylPdcomplex 13 was added dropwise to the solution of ^(TEOS)IPr 6. Theresulting solution was stirred at room temperature for 1.5 hour. Beforeand after the stirring, the color of the solution was changed from brownto black. Next, the solution was passed through a powder of activatedcarbon to remove the Pd black produced by the reaction. The color of thesolution was changed to yellow after passing through the activatedcarbon. Next, THF was completely removed from the resulting solution.Next, a small amount of dehydrated hexane was added and powdered. Theresulting solid was washed with hexane to give a white solid {reactionproduct 16 in the reaction scheme (R8), i.e., ^(TEOS)IPrPd(allyl)}.

[Comparative Example 1 Fourth Step] Purification of OrganometallicComplex Catalyst Obtained after Third Step

After the third step, with respect to the yellow solid{^(TEOS)IPrPd(allyl) 16}, the purification was performed by subjectingto recrystallization treatment by using hexane etc.

Incidentally, this ^(TEOS)IPrPd(allyl) 16 was synthesized for the firsttime by the present inventors as the organometallic complex catalystused for the cross-coupling reaction.

The yielded amount of ^(TEOS)IPrPd(allyl) 16 (white powder solid) was2.53 g, and the yield was 42.8%.

Comparative Example 1 Identification

The ^(TEOS)IPrPd(allyl) 16 was identified by ¹H NMR, ¹³C{¹H} NMR,²⁹Si{H} NMR, MALDI-TOF-MS and elemental analysis.

The measurement results of the ^(TEOS)IPrPd(allyl) 16 are shown below.

FIG. 6 shows the spectrum of ¹H NMR obtained for the organometalliccomplex catalyst {^(TEOS)IPrPd(allyl) 16} of Comparative Example 1. FIG.7 shows the spectrum of MALDI-TOF-MS obtained for the organometalliccomplex catalyst {^(TEOS)IPrPd(allyl) 16} of Comparative Example 1.Table 2 shows the results of the elemental analysis.

¹H NMR ¹H NMR (CDCl₃, 400 MHz): δ7.39-7.36 (m, 2H), 7.37 (s, 1H),7.28-7.20 (m, 4H), 4.76 (m, 1H), 3.92 (d, 1H, J=7.4 Hz), 3.58 (q, 6H),3.05 (m, 3H), 2.94 (m, 1H), 2.81 (d, 1H, J=13.6 Hz), 2.63 (m, 1H), 1.52(d, 1H, J=11.8 Hz), 1.42-1.15 (m, 24H), 1.03 (t, 9H, J=7.0 Hz)

¹³C{¹H} NMR (CDCl₃, 100 MHz): δ190.3, 146.8, 146.5, 145.8, 145.5, 137.6,135.9, 135.3, 129.8, 129.3, 128.1, 124.3, 124.0, 123.7, 114.2, 72.9,58.8, 50.4, 28.8, 28.7, 28.4, 26.6, 25.8, 25.4, 25.1, 24.8, 23.4, 17.9

²⁹Si{¹H} NMR (CDCl₃, 80 MHz): δ −68.6

TABLE 2 C₃₆H₅₅ClN₂PdSi C [%] H [%] N [%] Calculated value 58.93 7.563.82 Measured value 59.07 7.51 3.77

From the results of ¹H NMR, with respect to ^(TEOS)IPrPd(allyl) 16, apeak derived from the allyl group was observed, and the integrated valuewas consistent with the desired structure. In addition, one clean signalwas observed from the ²⁹Si{¹H} NMR. The detailed assignment of ¹H NMRand ¹³C {¹H} NMR are determined by ¹H-¹H correlation, ¹H-¹³Ccorrelation, ¹³C DEPT spectrum.

As shown in Table 2, it is determined that the desired compound^(TEOS)IPrPd(allyl) 16 was synthesized, because the calculated value andthe measured value according to the elementary analysis are almostidentical (difference within 0.3%).

Further, from the results of MALDI-TOF-MS shown in FIG. 7, it wasobserved that Cl was removed from Pd by a laser. The result ofMALDI-TOF-MS suggests that the ligand having the NHC structure is boundto Pd, and from this viewpoint as well, it was judged that the desired^(TEOS)IPrPd(allyl) could be synthesized.

Example 2

The organometallic complex catalyst represented by the formula (4){trade name “NVNL-PDA”, available from N.E. CHEMCAT CORPORATION wasprepared.

The organometallic complex catalyst of Example 2 was synthesizedaccording to the following procedure.

[Example 2 First Step-1] Synthesis of Ligand “IPr” Having the NHCStructure

The IPr was synthesized according to the same procedures andidentification methods as in the procedures and identification methodsdescribed in [Example 1 First Step-1] of Example 1.

[Example 2 First Step-2] Synthesis of Ligand Having Silyl Group(—SiMe₂C₃H₅) Group Bonded to Carbon at 4-Position in NHC Structure ofIPr

A ligand {ligand represented by the following formula (9)} having theNHC structure which was used in Example 2 represented by the formula (4)was synthesized by using the ligand IPr obtained in the aforementioned[First Step-1].

Specifically, through the two steps represented by the followingreaction scheme (R9), synthesis of the ligand represented by the formula(9) where the silyl group (—SiMe₂C₃H₅) is bonded to the carbon at4-position in the NHC structure of IPr (reactant 3).

In the reaction scheme (R9), nBuLi represents CH₃CH₂CH₂CH₂Li, and THFrepresents tetrahydrofuran.

The intermediate product 4 (Li—IPr) in the reaction scheme (R9) wassynthesized according to the same synthesis procedures as the synthesisprocedures of the intermediate product 4 (Li—IPr) in the reaction scheme(R4) described in [Example 1 First Step-2] of Example 1.

Next, the synthesis procedure of the reaction product in the reactionscheme (R9), that is, the desired ligand where the silyl group(—SiMe₂C₃H₅) is bonded to the carbon at 4-position in the NHC structureof the ligand IPr) is explained.

Firstly, a predetermined amount of the intermediate product (Li—IPr) inthe reaction scheme (R9) and a predetermined amount of dehydrated THFwere added and dissolved in a 100 mL eggplant flask in a glove box.Next, a predetermined amount of ClSiMe₂C₃H₅ was slowly added dropwise,allowed to react for a predetermined period of time. After thecompletion of the reaction, the solvent was removed.

In a glove box, a predetermined amount of dehydrated hexane was added tothe reaction product in the reaction scheme (R9) and transferred to acentrifuge tube. The centrifuging was carried out at 4000 rpm for apredetermined period of time at room temperature to separate the salt(LiCl). Next, the obtained filtrate was passed through a filter(available from advantec Co., Ltd., 0.2 μm) and separated into a 50 mLSchlenk. Next, the solvent was removed to obtain the reaction product inthe reaction scheme (R9), that is, the desired ligand.

Identification was carried out by using ¹H NMR, ¹³C{¹H} NMR,²⁹Si{¹H}NMR, and it was confirmed that the lithiation of the hydrogenatom bonded to the carbon at the 4-position in the NHC structure of IPr(reactant 3) proceeds, and the reaction product in the reaction scheme(R9) (desired ligand) was synthesized.

The ¹H NMR spectra obtained for the reaction product in the reactionscheme (R9) (ligand) having the NHC structure is shown in FIG. 8.

Measurement results of the reaction product in the reaction scheme (R9),that is, the desired ligand where the silyl group (—SiMe₂C₃H₅) is bondedto the carbon at 4-position in the NHC structure of the ligand IPr isshown below.

¹H NMR (THF-d8, 400 MHz): δ 7.43-7.37 (m, 2H), 7.33 (s, 1H), 7.31-7.28(m, 4H), 5.77-5.66 (m, 1H), 4.84-4.80 (m, 2H), 2.86 (sept, J=6.9 Hz,2H), 2.71 (sept, J=6.8 Hz, 2H), 1.60 (d, J=8.0 Hz, 2H), 1.33 (d, J=6.9Hz, 6H), 1.23-1.19 (m, 18H), −0.04 (s, 6H) ppm

¹³C{¹H} NMR (THF-d8, 100 MHz) δ 222.7, 146.1, 145.7, 139.7, 138.4,134.0, 131.3, 129.5, 128.4, 128.2, 123.0, 122.7, 113.1, 28.5, 28.1,25.4, 23.7, 23.6, 23.2, 21.2, −3.5 ppm

²⁹Si{¹H} NMR (THF-d8, 80 MHz): δ −11.8 ppm

From the results of ¹H NMR shown in FIG. 8, it was confirmed that thedesired ligand where the silyl group (—SiMe₂C₃H₅) is bonded to thecarbon at 4-position in the NHC structure of the ligand IPr wassynthesized.

[Example 2 Second Step] Synthesis of Complex Containing CoordinationCenter M, Halogen X, and Substituent R⁸

According to the reaction represented by the following reaction scheme(R5), The π-allylPd complex 13 {[(allyl)PdCl₂]₂} was synthesizedaccording to the same procedures and identification methods as in theprocedures and identification methods described in [Example 1 SecondStep] of Example 1.

[Example 2 Third Step] Reaction of Ligand Having the NHC StructureObtained in the First Step with the Complex Obtained in the Second Step>

The organometallic complex catalyst of Example 2 was synthesized,according to the following reaction scheme (R10), by reacting the ligandhaving the NHC structure obtained in the first step with the π-allylPdcomplex {[(allyl)PdCl₂]₂} obtained in the second step.

In the third step, the reaction conditions are independently examined bythe present inventors.

In a glove box, a predetermined amount of the ligand having the NHCstructure obtained in the first step and a predetermined amount ofdehydrated THF were added to a 50 mL Schlenk. Next, a predeterminedamount of the π-allylPd complex {[(allyl)PdCl₂]₂} obtained in the secondstep and a predetermined amount of dehydrated THF were added to a 50 mLvial. The solution of the n-allylPd complex was added dropwise to thesolution of the ligand having the NHC structure. The resulting solutionwas stirred at room temperature for a predetermined period of time.

Next, the solution was passed through a powder of activated carbon toremove the Pd black produced by the reaction. The color of the solutionwas changed to yellow after passing through the activated carbon. Next,THF was completely removed from the resulting solution. Next, a smallamount of dehydrated hexane was added and powdered. The resulting solidwas washed with hexane to give the reaction product in the reactionscheme (R10).

[Example 2 Fourth Step] Purification of Organometallic Complex CatalystObtained after Third Step

After the third step, with respect to the reaction product in thereaction scheme (R10), the purification was performed by subjecting torecrystallization treatment by using hexane etc. to obtain theorganometallic complex catalyst of Example 2.

Incidentally, this organometallic complex catalyst of Example 2 wassynthesized for the first time by the present inventors as theorganometallic complex catalyst used for the cross-coupling reaction.

Example 2 Identification

The organometallic complex catalyst of Example 2 was identified by ¹HNMR, ¹³C{¹H} NMR, ²⁹Si{¹H} NMR, MALDI-TOF-MS and elemental analysis. Themeasurement results thereof are shown below.

FIG. 9 shows the spectrum of ¹H NMR obtained for the organometalliccomplex catalyst of Example 2.

¹H NMR (C₆D₆, 400 MHz): δ 7.26-7.22 (m, 1H), 7.18-7.14 (m, 3H), 7.09 (s,1H), 7.07-7.01 (m, 2H), 5.70-5.59 (m, 1H), 4.88-4.84 (m, 2H), 4.47-4.37(m, 1H), 3.84-3.82 (m, 1H), 3.44-3.30 (m, 3H), 3.01-2.95 (m, 2H), 2.75(d, J=13.5 Hz, 1H), 1.60 (d, J=11.9 Hz, 1H), 1.54-1.52 (m, 5H), 1.49 (d,J=6.6 Hz, 3H), 1.39 (d, J=6.7 Hz, 3H), 1.34 (d, J=6.6 Hz, 3H), 1.13-1.10(m, 9H), 1.03 (d, J=6.9 Hz, 3H), −0.13 (s, 6H) ppm

¹³C{¹H} NMR (C₆D₆, 100 MHz) δ 190.4, 146.7, 146.1, 145.6, 137.6, 136.4,133.8, 133.3, 133.2, 129.7, 129.6, 124.2, 123.8, 123.5, 114.6, 113.4,72.1, 49.6, 28.8, 28.6, 28.1, 28.0, 26.3, 25.5, 25.0, 24.6, 24.5, 23.3,22.6, −2.9, −3.0 ppm

²⁹Si{¹H} NMR (C₆D₆, 80 MHz): δ −9.9 ppm

The result of ¹H NMR shown FIG. 9, it was judged that the reactionproduct in the reaction scheme (R10), that is, the organometalliccomplex catalyst of Example 2 could be synthesized.

Comparative Example 2

A commercially available organometallic complex catalyst represented bythe following formula (10) {trade name“allyl[1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]chloropalladium(II)”,available from Aldrich (hereinafter referred to as “IPrPd(allyl)” asoccasion demand)} was prepared.

<X-Ray Crystal Structure Analysis>

Since the single crystals of Example 1 and Comparative Example 1 couldbe prepared, X-ray crystal structure analysis was performed.

Each product of Example 1 and Comparative Example 1 was dissolved inhexane, and the resulting solution was recrystallized by cooling fromroom temperature to −40° C.

FIG. 10 shows ORTEP (Oak Ridge Thermal Ellipsoid Plot) obtained for theorganometallic complex catalyst of Example 1.

FIG. 11 shows ORTEP obtained for the organometallic complex catalyst ofComparative Example 1. FIG. 12 shows ORTEP obtained for theorganometallic complex catalyst of Example 1 and the organometalliccomplex catalyst of Comparative Example 1.

Table 3 shows bond distances and bond angles obtained for each of theconstituent atoms that constitute Example 1 shown in FIG. 10. Further,Table 4 shows bond distances and bond angles obtained for each of theconstituent atoms that constitute Comparative Example 1 shown in FIG.11.

Furthermore, with respect to the crystal structure analysis data ofExample 1 and Comparative Example 1, the main description itemsdescribed in the CIF file defined by the International Union ofCrystallography (International Union of Crystallography) IUCr are shownin Table 5.

TABLE 3 Example 1 ^(TMS)IPrPd(allyl) 15 Bond distances and bond anglesobtained for each of the constituent atoms shown in FIG. 10 Bonddistance (Å) Bond angle (°) Pd(1)—C(1) 2.040(2) Cl(1)—Pd(1)—C(1) 94.34(6) Pd(1)—C(2) 2.208(3) C(1)—Pd(1)—C(5) 100.36(12) Pd(1)—C(3)2.151(6) Pd(1)—C(1)—N(1) 127.79(15) Pd(1)—C(4) 2.165(7) Pd(1)—C(1)—N(2)128.01(14) Pd(1)—C(5) 2.116(4) Si(1)—C(6)—N(1) 131.93(15) Pd(1)—Cl(1)2.361(8) Si(1)—C(6)—C(7) 124.07(17) C(1)—N(1) 1.360(3) C(1)—N(1)—C(11)123.97(17) C(1)—N(2) 1.359(3) C(1)—N(2)—C(23) 125.21(17) Si(1)—N(6)1.899(2)

TABLE 4 Comparative Example 1 ^(TEOS)IPrPd(allyl) 16 Bond distances andbond angles obtained for each of the constituent atoms shown in FIG. 11Bond distance (Å) Bond angle (°) Pd(1)—C(1) 2.055(16) Cl(1)—Pd(1)—C(1) 94.69(4) Pd(1)—C(2) 2.119(2) C(1)—Pd(1)—C(2) 101.75(7) Pd(1)—C(3)2.159(6) Pd(1)—C(1)—N(1) 125.93(11) Pd(1)—C(4) 2.137(4) Pd(1)—C(1)—N(2)129.56(11) Pd(1)—C(5) 2.183(3) Si(1)—C(6)—N(1) 129.91(11) Pd(1)—Cl(1)2.363(4) Si(1)—C(6)—C(7) 125.63(13) C(1)—N(1) 1.358(2) C(1)—N(2)—C(8)120.99(13) C(1)—N(2) 1.362(19) C(1)—N(2)—C(20) 125.88(14) Si(1)—N(6)1.861(17) Si(1)—O(1) 1.623(12)

TABLE 5 Example 1 Com. Example 1 ^(TMS)IPrPd(allyl) ^(TEOS)IPrPd(allyl)Name of data 15 16 Chemical Chemical C₃₃H₄₉ClN₂PdSi C₃₆H₅₅ClN₂PdSiformula formula Molecular Formula weight 643.7240 733.78 weightTemparature Temperature, K 90 90 Characteristic Wavelength, Å 0.710690.71069 X-ray wavelength Crystal system Crystal system monoclinicmonoclinic Space group Space group P-1 P-1 Unit lattice a, Å 10.4846(5)18.1934(9) parameter b, Å 16.0964(8) 13.2031(6) c, Å 19.7252(10)16.3077(8) α, deg β, deg 93.994(1) 102.449(1) γ, deg Unit lattice V, Å³3320.8(3) 3825.2(4) volume Number of Z 4 4 asymmetrical unit in unitlattice Linear μ, cm⁻¹ 6.99 6.21 absorption coefficient Crystal F(000)1352 1544 structural factor Calculation Deaied, g cm⁻³ 1.277 1.265density Crystal size Crystal size, mm 0.40 × 0.30 × 0.20 0.40 × 0.30 ×0.30 Number of No. of data 36245 41507 measured data Number of No. ofunique 7335 8421 measured data data Number of No. of variables 352 406optimized parameter R factor R(1 > 2 σ (I)) 0.0264 0.0172 R factor R(Allreflections) 0.0312 0.0222 Rw factor Rw(All 0.0821 0.0614 reflections) Svalue GOF 1.071 1.060 (Goddness of Fit)

From the results of the crystal structure analysis of Example 1 andComparative Example 1 described above, it has been confirmed that theTMS group was bonded to the carbon at the 4-position of the imidazolering which constituted the organometallic complex catalyst{^(TMS)IPrPd(allyl) 15} of Example 1, and that the TEOS group was bondedto the carbon at the 4-position of the imidazole ring which constitutedthe organometallic complex catalyst {^(TEOS)IPrPd(allyl) 16} ofComparative Example 1.

From the results shown in Table 3 and Table 4, for the organometalliccomplex catalyst {^(TMS)IPrPd(allyl) 15} of Example 1 and theorganometallic complex catalyst {^(TEOS)IPrPd(allyl) 16} of ComparativeExample 1, with respect to the bonding distance between the carbenecarbon of the imidazole ring and Pd, there was no significantlydifference between the two complexes.

Provided that, it can be seen that the bond angle θ of C(1)-N(1)-C(1) inthe organometallic complex catalyst {^(TMS)IPrPd (allyl) 15} of Example1 (see the bond angle θ1 shown in ORTEP of Example 1 in FIG. 12) issmaller by about 1° to 5° as compared with the angle at the sameposition on the opposite side (see Table 3 and FIG. 12).

In addition, it can be seen that the bond angle θ of C(1)-N(1)-C(8) inthe organometallic complex catalyst {^(TEOS)IPrPd (allyl) 16} ofComparative Example 1 (see the bond angle θ2 shown in ORTEP ofComparative Example 1 in FIG. 12) is smaller by about 1° to 5° ascompared with the angle at the same position on the opposite side (seeTable 4 and FIG. 12).

Furthermore, with respect to the organometallic complex catalyst ofExample 1 and the organometallic complex catalyst of Comparative Example1, when viewed from the direction perpendicular to the plane of theimidazole ring, it has been found that the substituent on the nitrogenwhich was located closer to the TEOS group among in the nitrogen atomsconstituting the imidazole ring was more largely distorted as a whole inthe organometallic complex catalyst of Comparative Example 1 comparedwith the organometallic complex catalyst of Example 1, due to the effectof bonding of the TEOS group {(EtO)₃Si group} (effect of sterichindrance) (see FIG. 12, ORTEP of Comparative Example 1).

Example 1-Rh

The organometallic complex catalyst {trade name “NTMS-RHA”, availablefrom N.E. CHEMCAT CORPORATION} was prepared. This Example 1-Rh relatesto a catalyst having a configuration where the Pd of the coordinationcenter of the aforementioned organometallic complex catalyst of Example1 is substituted by Rh.

Example 1-Rh First Step

Firstly, the ligand having the NHC structure represented by theaforementioned formula (7) was synthesized by carrying out the samesynthesis procedure and analysis as in Example 1.

Example 1-Rh Second Step

Next, as the π-allylPd complex for a Rh source, a [Rh(CO)₂Cl]₂commercially available from Aldrich was prepared.

Example 1-Rh Third Step

Next, the organometallic complex catalyst of Example 1-Rh wassynthesized, according to the following reaction scheme (R11), byreacting the ligand represented by the formula (7) having the NHCstructure obtained in the first step with the π-allylRh complex obtainedin the second step.

Example 1-Rh Fourth Step

Purification of Organometallic Complex Catalyst Obtained after ThirdStep

After the third step, with respect to the solid containing the reactionproduct in the reaction scheme (R11), the purification was performed bysubjecting to recrystallization treatment by using hexane etc.

Example 1-Rh Identification

The reaction product of the reaction scheme (R11), that is, theorganometallic complex catalyst of Example 1-Rh {trade name “NTMS-RHA”,available from N.E. CHEMCAT CORPORATION} was identified and confirmed by¹H NMR, ¹³C{¹H} NMR, ²⁹Si{¹H} NMR, MALDI-TOF-MS and elemental analysis.

Example 2-Rh

The organometallic complex catalyst {trade name “NVNL-RHA”, availablefrom N.E. CHEMCAT CORPORATION} was prepared. This Example 2-Rh relatesto a catalyst having a configuration where the Pd of the coordinationcenter of the aforementioned organometallic complex catalyst of Example2 is substituted by Rh.

Example 2-Rh First Step

Firstly, the ligand having the NHC structure represented by theaforementioned formula (9) was synthesized by carrying out the samesynthesis procedure and analysis as in Example 1.

Example 2-Rh Second Step

Next, as the n-allylPd complex for a Rh source, a [Rh(CO)₂Cl]₂commercially available from Aldrich was prepared.

Example 2-Rh Third Step

Next, the organometallic complex catalyst of Example 2-Rh wassynthesized, according to the following reaction scheme (R12), byreacting the ligand represented by the formula (9) having the NHCstructure obtained in the first step with the n-allylRh complex obtainedin the second step.

Example 2-Rh Fourth Step

Purification of Organometallic Complex Catalyst Obtained after ThirdStep

After the third step, with respect to the solid containing the reactionproduct in the reaction scheme (R12), the purification was performed bysubjecting to recrystallization treatment by using hexane etc.

Example 2-Rh Identification

The reaction product of the reaction scheme (R12), that is, theorganometallic complex catalyst of Example 2-Rh {trade name “NVNL-RHA”,available from N.E. CHEMCAT CORPORATION} was identified and confirmed by¹H NMR, ¹³C{¹H} NMR, ²⁹Si{¹H} NMR, MALDI-TOF-MS and elemental analysis.

Comparative Example 1-Rh

The organometallic complex catalyst {trade name “NTEOS-RHA”, availablefrom N.E. CHEMCAT CORPORATION} was prepared. This Comparative Example1-Rh relates to a catalyst having a configuration where the Pd of thecoordination center of the aforementioned organometallic complexcatalyst (trade name “NTEOS-PDA”) of Comparative Example 1 issubstituted by Rh.

Comparative Example 1-Rh First Step

Firstly, the ligand (^(TEOS)IPr) having the NHC structure represented bythe aforementioned formula (8) was synthesized by carrying out the samesynthesis procedure and analysis as in Comparative Example 1.

Comparative Example 1-Rh Second Step

Next, as the π-allylPd complex for a Rh source, a [Rh(CO)₂Cl]₂commercially available from Aldrich was prepared.

Comparative Example 1-Rh Third Step

Next, the organometallic complex catalyst (trade name “NTEOS-RHA”) ofComparative Example 1-Rh was synthesized, according to the followingreaction scheme (R13), by reacting the ligand (^(TEOS)IPr) representedby the formula (8) having the NHC structure obtained in the first stepwith the r-allylRh complex obtained in the second step.

Comparative Example 1-Rh Fourth Step

Purification of Organometallic Complex Catalyst Obtained after ThirdStep

After the third step, with respect to the solid containing the reactionproduct in the reaction scheme (R13), the purification was performed bysubjecting to recrystallization treatment by using hexane etc.

Comparative Example 1-Rh Identification

The reaction product of the reaction scheme (R13), that is, theorganometallic complex catalyst of Comparative Example 1-Rh {trade name“NTEOS-RHA” } was identified and confirmed by ¹H NMR, ¹³C{¹H} NMR,²⁹Si{H} NMR, MALDI-TOF-MS and elemental analysis.

Comparative Example 2-Rh

The organometallic complex catalyst (hereinafter, referred to as “IPrRh”as occasion demand) where the Pd of the coordination center of thecommercially available organometallic complex catalyst represented bythe aforementioned formula (10) {trade name“allyl[1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene]chloropalladium(II)”, available from Aldrich, “IPrPd(allyl)”)} was substituted by Rhwas prepared. This Comparative Example 2-Rh relates to a catalyst havinga configuration where the Pd of the coordination center of theaforementioned organometallic complex catalyst of Comparative Example 2is substituted by Rh.

Comparative Example 2-Rh First Step

Firstly, the ligand IPr having the NHC structure represented by theaforementioned formula (P5) was synthesized by carrying out the samesynthesis procedure and analysis as in the first step-1 of Example 1.

Comparative Example 2-Rh Second Step

Next, as the n-allylPd complex for a Rh source, a [Rh(CO)₂Cl]₂commercially available from Aldrich was prepared.

Comparative Example 2-Rh Third Step

Next, the organometallic complex catalyst IPrRh of Comparative Example2-Rh was synthesized, according to the following reaction scheme (R14),by reacting the ligand IPr represented by the formula (P5) having theNHC structure obtained in the first step with the n-allylRh complexobtained in the second step.

Comparative Example 2-Rh Fourth Step

Purification of Organometallic Complex Catalyst Obtained after ThirdStep

After the third step, with respect to the solid containing the reactionproduct IPrRh in the reaction scheme (R14), the purification wasperformed by subjecting to recrystallization treatment by using hexaneetc.

Comparative Example 2-Rh Identification

The reaction product of the reaction scheme (R14), that is, theorganometallic complex catalyst IPrRh of Comparative Example 2-Rh wasidentified and confirmed by ¹H NMR, ¹³C{¹H} NMR, ²⁹Si{¹H} NMR,MALDI-TOF-MS and elemental analysis.

<IR Measurement of Example 1-Rh, Example 2-Rh, Comparative Example 1-Rh,Comparative Example 2-Rh>

With respect to the organometallic complex catalysts of Example 1-Rh,Example 2-Rh, Comparative Example 1-Rh, and Comparative Example 2-Rh,infrared absorption spectra were measured. Then, by using the arithmeticmean value of the stretching frequency [cm⁻¹] of the carbonyl groupobtained from each infrared absorption spectrum, according to thefollowing formula (E1) described above, the TEP value [cm⁻¹] of theorganometallic complex catalyst where the coordination center wassubstituted from Rh to Ni was calculated.

[Equ. 3]

TEP[cm⁻¹]=ν_(CO) ^(av/Ni) [cm⁻¹]=0.8001ν_(CO) ^(av/Rh) [cm⁻¹]+420.0[cm⁻¹]  (E1)

The TEP values of the respective organometallic complex catalysts areshown in Table 6.

TABLE 6 Arithmetic Stretching mean value frequency of of stretchingcarbonyl group frequency of of Ni complex Trade name carbonyl groupcalculated from or of Rh complex Equation E1 abbreviation νCO^(av)/Rh/cm⁻¹ TEP/cm^(−1 a) Example 1-Rh NTEMS-RHA 2024.9 2040.1(−3.5) Example 2-Rh NVNL-RHA 2022.0 2037.8 (−5.8) Com. NTEOS-PDA 2034.12047.4 (+3.9) Example 1-Rh Com. IPrRh 2029.2 2043.6 Example 2-Rh *^(a)Numerals in parentheses indicate the difference between the TEP value ofComparative Example 2-Rh and the TEP value of each organometalliccatalyst.

As is clear from the results shown in Table 6, it is confirmed that theTEP values of the organometallic complex catalyst of Example 1-Rh andExample 1-Rh are shifted to the lower wave number side than the TEPvalue of Comparative Example 2-Rh. That is, it has been found that theorganometallic complex catalysts of Example 1-Rh and Example 1-Rhinclude the ligand having the NHC structure which has a higher electrondonating property than the IPr ligand (formula (P5)) of ComparativeExample 2-Rh.

From this, it has been found that the organic metal complex catalysts ofExample 1 and Example 2 where the coordination center is substitutedfrom Rh to Pd also include the ligand having the NHC structure which hasa higher electron donating property than the IPr ligand (formula (P5))of Comparative Example 2.

<Catalytic Activity Evaluation (1) by Cross-Coupling Reaction>

By using the organometallic complex catalysts of Example 1, Example 2,Comparative Example 1 and Comparative Example 2, the C—N cross-couplingreaction (Buchwald-Hartwig reaction) represented by the followingreaction scheme (R15) was carried out.

As shown in reaction scheme (R15), there were used chlorobenzene,N,N-dibutylamine as a substrate, ^(t)BuOK as a base, and 1 mL of1,2-dimethoxyethane (DME) as a solvent. The preparation and reactionwere all carried out in an inert gas (Ar) atmosphere in a glove box. Theyield was calculated by GC by using dodecane and mesitylene as aninternal standard substance.

The reaction conditions were that, with respect to 1 mmol ofchlorobenzene, N,N-dibutylamine was 1.7 mmol, a temperature was 70° C.and an amount of the catalyst was 0.10 mol %. Table 7 shows the resultsof the catalytic activity evaluation of the organometallic complexcatalysts of Example 1, Example 2, Comparative Example 1, andComparative Example 2.

TABLE 7 Yield per reactiontime/% Trade name 10 min 30 min 60 min 90 minEx. 1 NTEMS-PDA 13 64 100 100 Ex. 2 NVNL-PDA 17 80 99 100 Com. Ex. 1NTEOS-PDA 10 28 95 99 Com. Ex. 2 Ipr 10 31 92 95

From the results shown in Table 7, when using the organometallic complexcatalysts of Example 1 and Example 2 which satisfy the features of thepresent invention in comparison with the organometallic complex catalystof Comparative Example 2 which is the commercially available product, ithas been clear that the desired product can be obtained in very highyield for the C—N cross-coupling reaction.

It has been clear that the organometallic complex catalysts of Example 1and Example 2 which satisfy the features of the present invention cangive the desired product in a higher yield than the organometalliccomplex catalysts of Comparative Example 2 and Comparative Example 1even in a short reaction time.

<Catalytic Activity Evaluation (2) by Cross-Coupling Reaction>

By using the organometallic complex catalysts of Example 2 andComparative Example 2, the C—N cross-coupling reaction represented bythe following reaction scheme (R16) was carried out.

As shown in reaction scheme (R16) and the following Table 7-2, therewere used various aryl chlorides and morpholine as a substrate, ^(t)BuOKas a base, and 2 mL of 1,2-dimethoxyethane (DME) as a solvent. Thepreparation and reaction were all carried out in an inert gas (Ar)atmosphere in a glove box. The yield was calculated by GC by usingdodecane and mesitylene as an internal standard substance.

The reaction conditions were that, with respect to 1 mmol of variousaryl chlorides, morpholine was 1.7 mmol, a temperature was 70° C. and anamount of the catalyst was 0.10 mol %. Table 8 shows the results of thecatalytic activity evaluation of the organometallic complex catalysts ofExample 2 and Comparative Example 1.

TABLE 8 Catalyst [Pd] Substituent [R] in formula R16 in formula R16Yield ^(a)/% Conv. ^(a)/% Example 2 H 89 91 Com. Example 2 H 77 80Example 2 OMe 73 79 Com. Example 2 OMe 47 50 Example 2 CN 3 69 Com.Example 2 CN 3 67 *^(a) GC yield/conversion

From the results shown in Table 8, when using the organometallic complexcatalyst of Example 2 which satisfies the features of the presentinvention in comparison with the organometallic complex catalyst ofComparative Example 2 which is the commercially available product, ithas been clear that the desired product can be obtained in very highyield and conversion for every C—N cross-coupling reaction of the threearyl chlorides and morpholine.

In general, in a cross-coupling reaction, the reaction is initiated fromoxidative addition where palladium having a lot of electrons gives anelectron to an aryl halide to cleave the C—X bond (X is a halogen atom)(e.g., see “Akio Yamamoto, Organometallic Complex, Shokabou”).Therefore, it can be suspected that the oxidative addition is promotedby increasing the electron density of palladium.

However, as in the reaction mechanism shown in FIG. 14, in the C—Ncoupling reaction as in the reaction scheme (R15) and the reactionscheme (16), it has been clear that the rate-limiting step in the caseof using a bulky ligand is the step of coordination of an amine to ametal or a step of abstraction of a proton by a base (see, for example,the academic article “a) Organ. M. G., Abdel-Hadi, M., Avola, S.,Dubovyk, I., Hadei, N., Kantchev, E. A. B., Obrien, C. J., Valente, C.Chem. Eur. J. 2008, 14, 2443 b) Hoi, K. H., Calimsiz, S., Froese, R. D.J., Hopkinson, A. C., Organ, M. G. Chem. Eur. J. 2011, 17, 3086 c)Ikawa, T., Barder, T. E., Biscoe, M. R., Buchwald, S. L. J. Am. Chem.Soc. 2007, 129, 13001”).

Here, FIG. 14 is a conceptual diagram which shows the reaction mechanismclarified in the C—N coupling reaction where an organic Pd complexcatalyst is used (see the aforementioned academic articles a) to c)).

That is, the present inventors understand that the rate-limiting step inthe C—N coupling reaction is the step of coordination of the amine tothe metal or the step of abstraction of the proton on the amine, whenemploying the structure where the silyl group is bonded to the carbon atthe 4-position in the imidazole ring, and the structure where the TEPvalue satisfies the conditions described above, the electron density onPd is increased to leads to the stabilization of the catalyticallyactive species Pd⁰ (stabilization of the catalyst).

INDUSTRIAL APPLICABILITY

The catalyst of the present invention can give a higher yield of thedesired object than conventional catalysts in a cross-coupling reaction.Thus, the present invention contributes to the development of massproduction techniques in the fields of medicines, pesticides andelectronic materials where cross-coupling is available for the synthesisof the desired products (e.g. aromatic amines).

According to the ligand of the present invention, it is possible toprovide the organometallic complex catalyst capable of obtaining ahigher yield of the desired product than the conventional catalysts inthe cross-coupling reaction.

Further, according to the present invention, a method for reliablypreparing the organometallic complex catalyst for the cross-couplingreaction where the ligand is used, that is, the organometallic complexcatalyst which can give the desired product in a higher yield than theconventional catalysts in the cross-coupling reaction can be provided.

Thus, the present invention contributes to the development of massproduction techniques in the fields of medicines, pesticides andelectronic materials where cross-coupling is available for the synthesisof the desired products (e.g. aromatic amines).

EXPLANATION OF SYMBOLS

-   15 ^(TMS)IPrPd(allyl)-   16 ^(EOS)IPrPd(allyl)-   IPr 1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene-   NHC Nitrogen-containing heterocyclic carbene (N-Heterocyclic    Carbene)-   TEOS Triethoxysilyl group-   TMS Trimethylsilyl group

1. A ligand which comprises a nitrogen-containing heterocyclic carbenestructure represented by the following formula (2) and is a structuralmaterial of an organometallic complex catalyst for use in across-coupling reaction having a structure represented by the followingformula (1).

wherein, in the formulae (1) and (2), M is a coordination center andrepresents any one of metal atoms selected from the group consisting ofPd, Pt, Rh, Ru and Cu, or an ion thereof; R¹, R² and R³ is optionallythe same or different, and each represents at least one substituentselected from the group consisting of a hydrogen atom, an alkyl group,an alkoxy group, alkenyl group, an alkynyl group and an aryl group; R⁴,R⁵, R⁶ and R⁷ is optionally the same or different, and each representsat least one substituent selected from a hydrogen atom, a halogen atom,an alkyl group, an alkoxy group, an alkenyl group, an alkynyl group, anaryl group, a hydroxy group, hydroxylate group, a thiocarboxyl group, adithiocarboxyl group, a sulfo group, a sulfino group, an oxycarbonylgroup, a carbamoyl group, a hydrazinocarbonyl group, an amidino group, acyano group, an isocyano group, a cyanato group, an isocyanato group, athiocyanato group, an isothiocyanato group, a formyl group, an oxogroup, a thioformyl group, a thioxo group, a mercapto group, an aminogroup, an imino group, a hydrazino group, an aryloxy group, a sulfidegroup, a nitro group and a silyl group; X represents a halogen atomwhich is capable of coordinating to the coordination center M; R⁸represents a substituent having a π bond and 3 to 20 carbon atoms whichis capable of coordinating to the coordination center M; provided that,with regard to electron-donating property with respect to thecoordination center M, R¹, R², R³, R⁴, R⁵, R⁶ and R⁷ are so combined andarranged that a TEP value (Tolman electronic parameter) [cm⁻¹] obtainedby an infrared spectroscopy of a ligand having a nitrogen-containingheterocyclic carbene structure represented by the following formula (2)which contains R¹ to R⁷, sifts toward a low frequency side compared tothe TEP value [cm⁻¹] of a ligand represented by the formula (2-1).

wherein, in the formula (2-1), R⁴, R⁵, R⁶ and R⁷ represent the samesubstituents as R⁴, R⁵, R⁶ and R⁷ in the formula (1).
 2. The ligandaccording to claim 1, wherein the TEP value of the ligand having thenitrogen-containing heterocyclic carbene structure represented by thefollowing formula (2) is a value calculated from a stretching frequencyof a carbonyl group obtained from an infrared absorption spectrummeasured on an Rh carbonyl complex represented by the following formula(1-1), which is a complex where, in the formula (1), the portion of the-MR⁸X is substituted by —Rh(CO)₂Cl.


3. The ligand according to claim 1, wherein the organometallic complexcatalyst represented by the formula (1) is used in a C—N cross-couplingreaction.
 4. The ligand according to claim 1, wherein the organometalliccomplex catalyst represented by the formula (1) has a structurerepresented by any one of the following formula (3), the formula (4) orthe formula (5).

wherein, in the formulae (3) to (5), ^(i)Pr represents an isopropylgroup, Me represents methyl group.